CN111686134A - 一种益生菌组合物及其制备方法和用途 - Google Patents
一种益生菌组合物及其制备方法和用途 Download PDFInfo
- Publication number
- CN111686134A CN111686134A CN202010414426.7A CN202010414426A CN111686134A CN 111686134 A CN111686134 A CN 111686134A CN 202010414426 A CN202010414426 A CN 202010414426A CN 111686134 A CN111686134 A CN 111686134A
- Authority
- CN
- China
- Prior art keywords
- probiotic composition
- product
- auxiliary materials
- bifidobacterium
- jaundice
- 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.)
- Pending
Links
- 239000006041 probiotic Substances 0.000 title claims abstract description 61
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 60
- 239000000203 mixture Substances 0.000 title claims abstract description 46
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 45
- 238000002360 preparation method Methods 0.000 title claims description 9
- 238000001126 phototherapy Methods 0.000 claims abstract description 36
- 241000186000 Bifidobacterium Species 0.000 claims abstract description 35
- 241000186660 Lactobacillus Species 0.000 claims abstract description 33
- 206010023126 Jaundice Diseases 0.000 claims abstract description 26
- 239000002207 metabolite Substances 0.000 claims abstract description 10
- 239000000463 material Substances 0.000 claims description 18
- 241000186012 Bifidobacterium breve Species 0.000 claims description 14
- 235000013305 food Nutrition 0.000 claims description 13
- 238000002156 mixing Methods 0.000 claims description 13
- 241000186840 Lactobacillus fermentum Species 0.000 claims description 11
- 229940012969 lactobacillus fermentum Drugs 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 6
- 102000004407 Lactalbumin Human genes 0.000 claims description 5
- 108090000942 Lactalbumin Proteins 0.000 claims description 5
- 208000037817 intestinal injury Diseases 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- -1 /or Species 0.000 claims description 4
- 102000007544 Whey Proteins Human genes 0.000 claims description 4
- 108010046377 Whey Proteins Proteins 0.000 claims description 4
- 235000021255 galacto-oligosaccharides Nutrition 0.000 claims description 4
- 150000003271 galactooligosaccharides Chemical class 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 229940127557 pharmaceutical product Drugs 0.000 claims description 4
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 3
- 239000005913 Maltodextrin Substances 0.000 claims description 3
- 229920002774 Maltodextrin Polymers 0.000 claims description 3
- 239000005862 Whey Substances 0.000 claims description 3
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 3
- 235000013734 beta-carotene Nutrition 0.000 claims description 3
- 239000011648 beta-carotene Substances 0.000 claims description 3
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 3
- 229960002747 betacarotene Drugs 0.000 claims description 3
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 3
- 229960001231 choline Drugs 0.000 claims description 3
- 238000011278 co-treatment Methods 0.000 claims description 3
- 239000008101 lactose Substances 0.000 claims description 3
- 229940035034 maltodextrin Drugs 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002773 nucleotide Substances 0.000 claims description 3
- 125000003729 nucleotide group Chemical group 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 235000020183 skimmed milk Nutrition 0.000 claims description 3
- 235000015112 vegetable and seed oil Nutrition 0.000 claims description 3
- 239000008158 vegetable oil Substances 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 235000021241 α-lactalbumin Nutrition 0.000 claims description 3
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 3
- 239000002775 capsule Substances 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims description 2
- FTSSQIKWUOOEGC-RULYVFMPSA-N fructooligosaccharide Chemical class 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 claims description 2
- 229940107187 fructooligosaccharide Drugs 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 229960001375 lactose Drugs 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 208000028774 intestinal disease Diseases 0.000 claims 1
- 239000003921 oil Substances 0.000 claims 1
- 235000019198 oils Nutrition 0.000 claims 1
- 210000001035 gastrointestinal tract Anatomy 0.000 abstract description 23
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 10
- 201000010099 disease Diseases 0.000 abstract description 9
- 230000036039 immunity Effects 0.000 abstract description 3
- 208000027418 Wounds and injury Diseases 0.000 abstract description 2
- 230000006378 damage Effects 0.000 abstract description 2
- 208000014674 injury Diseases 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 32
- 239000011324 bead Substances 0.000 description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
- 239000003613 bile acid Substances 0.000 description 23
- 239000006228 supernatant Substances 0.000 description 20
- 238000006243 chemical reaction Methods 0.000 description 19
- 229940039696 lactobacillus Drugs 0.000 description 18
- 230000000968 intestinal effect Effects 0.000 description 13
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 12
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 11
- 210000003608 fece Anatomy 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- 238000012163 sequencing technique Methods 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 239000000523 sample Substances 0.000 description 9
- 230000002195 synergetic effect Effects 0.000 description 9
- 230000008859 change Effects 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 241000894007 species Species 0.000 description 8
- 241001134770 Bifidobacterium animalis Species 0.000 description 7
- 206010023138 Jaundice neonatal Diseases 0.000 description 7
- 229940118852 bifidobacterium animalis Drugs 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 6
- 230000002503 metabolic effect Effects 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 201000006346 Neonatal Jaundice Diseases 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000008280 blood Substances 0.000 description 5
- 210000004369 blood Anatomy 0.000 description 5
- 238000007664 blowing Methods 0.000 description 5
- 230000002596 correlated effect Effects 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- 241000193403 Clostridium Species 0.000 description 4
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
- 238000004140 cleaning Methods 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 238000007400 DNA extraction Methods 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000005906 dihydroxylation reaction Methods 0.000 description 3
- 230000002550 fecal effect Effects 0.000 description 3
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 235000021391 short chain fatty acids Nutrition 0.000 description 3
- 150000004666 short chain fatty acids Chemical class 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 241001608472 Bifidobacterium longum Species 0.000 description 2
- 108010000231 Choloylglycine hydrolase Proteins 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- 102000012410 DNA Ligases Human genes 0.000 description 2
- 108010061982 DNA Ligases Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 240000006024 Lactobacillus plantarum Species 0.000 description 2
- 235000013965 Lactobacillus plantarum Nutrition 0.000 description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 2
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 239000011543 agarose gel Substances 0.000 description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 230000003321 amplification Effects 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 235000008452 baby food Nutrition 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 238000010009 beating Methods 0.000 description 2
- 229940009291 bifidobacterium longum Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000010276 construction Methods 0.000 description 2
- 238000005336 cracking Methods 0.000 description 2
- 238000005138 cryopreservation Methods 0.000 description 2
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 description 2
- 229960002061 ergocalciferol Drugs 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000003292 glue Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 229940072205 lactobacillus plantarum Drugs 0.000 description 2
- 238000003199 nucleic acid amplification method Methods 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012521 purified sample Substances 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 239000013589 supplement Substances 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960003495 thiamine Drugs 0.000 description 2
- 235000001892 vitamin D2 Nutrition 0.000 description 2
- 239000011653 vitamin D2 Substances 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- 229940011671 vitamin b6 Drugs 0.000 description 2
- 238000003260 vortexing Methods 0.000 description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- FRIRHJVKXFYECW-ZTERCDMUSA-N 6,7-diketolithocholic acid Chemical compound C[C@H](CCC(O)=O)[C@H]1CC[C@H]2[C@H]3[C@H](CC[C@]12C)[C@@]1(C)CC[C@@H](O)C[C@H]1C(=O)C3=O FRIRHJVKXFYECW-ZTERCDMUSA-N 0.000 description 1
- UOELMDIOCSFSEN-FVZZCGLESA-N 7-Dehydrositosterol Chemical compound C1([C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)C=C[C@H](C)C(C)C)=CC=C1C[C@@H](O)CCC1=C.C1[C@@H](O)CCC2(C)C(CC[C@@]3([C@@H]([C@H](C)C=C[C@H](C)C(C)C)CC[C@H]33)C)C3=CC=C21 UOELMDIOCSFSEN-FVZZCGLESA-N 0.000 description 1
- 235000008658 Artemisia capillaris Nutrition 0.000 description 1
- 241000092668 Artemisia capillaris Species 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 108010062877 Bacteriocins Proteins 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000186011 Bifidobacterium catenulatum Species 0.000 description 1
- 241001134772 Bifidobacterium pseudocatenulatum Species 0.000 description 1
- 229910000906 Bronze Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- ARVGMISWLZPBCH-UHFFFAOYSA-N Dehydro-beta-sitosterol Natural products C1C(O)CCC2(C)C(CCC3(C(C(C)CCC(CC)C(C)C)CCC33)C)C3=CC=C21 ARVGMISWLZPBCH-UHFFFAOYSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- SPOIYSFQOFYOFZ-BRDORRHWSA-N Glycohyodeoxycholic acid Chemical compound C([C@H]1[C@@H](O)C2)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 SPOIYSFQOFYOFZ-BRDORRHWSA-N 0.000 description 1
- RTDFOQVLLJZRIH-JZAVHCKJSA-N Glycoursocholanic acid Chemical compound C([C@H]1CC2)CCC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCC(O)=O)C)[C@@]2(C)CC1 RTDFOQVLLJZRIH-JZAVHCKJSA-N 0.000 description 1
- 102100033969 Guanylyl cyclase-activating protein 1 Human genes 0.000 description 1
- 101001068480 Homo sapiens Guanylyl cyclase-activating protein 1 Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 240000001046 Lactobacillus acidophilus Species 0.000 description 1
- 235000013956 Lactobacillus acidophilus Nutrition 0.000 description 1
- 240000001929 Lactobacillus brevis Species 0.000 description 1
- 235000013957 Lactobacillus brevis Nutrition 0.000 description 1
- 244000199866 Lactobacillus casei Species 0.000 description 1
- 235000013958 Lactobacillus casei Nutrition 0.000 description 1
- 241000218492 Lactobacillus crispatus Species 0.000 description 1
- 241000218588 Lactobacillus rhamnosus Species 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 229930192627 Naphthoquinone Natural products 0.000 description 1
- 208000012902 Nervous system disease Diseases 0.000 description 1
- 208000025966 Neurological disease Diseases 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 206010047612 Vitamin B2 deficiency Diseases 0.000 description 1
- 229930003761 Vitamin B9 Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- DIPPFEXMRDPFBK-UHFFFAOYSA-N Vitamin D4 Natural products C1CCC2(C)C(C(C)CCC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C DIPPFEXMRDPFBK-UHFFFAOYSA-N 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 201000007590 ariboflavinosis Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 239000003858 bile acid conjugate Substances 0.000 description 1
- 238000003766 bioinformatics method Methods 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036983 biotransformation Effects 0.000 description 1
- 239000010974 bronze Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-BSWAIDMHSA-N 0.000 description 1
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- KUNSUQLRTQLHQQ-UHFFFAOYSA-N copper tin Chemical compound [Cu].[Sn] KUNSUQLRTQLHQQ-UHFFFAOYSA-N 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 235000000639 cyanocobalamin Nutrition 0.000 description 1
- 239000011666 cyanocobalamin Substances 0.000 description 1
- 229960002104 cyanocobalamin Drugs 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- JXTHNDFMNIQAHM-UHFFFAOYSA-N dichloroacetic acid Chemical compound OC(=O)C(Cl)Cl JXTHNDFMNIQAHM-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000010235 enterohepatic circulation Effects 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000005562 fading Methods 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 238000001502 gel electrophoresis Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000008821 health effect Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000012165 high-throughput sequencing Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 229940039695 lactobacillus acidophilus Drugs 0.000 description 1
- 229940068140 lactobacillus bifidus Drugs 0.000 description 1
- 229940017800 lactobacillus casei Drugs 0.000 description 1
- 230000020958 lipid digestion Effects 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 208000030159 metabolic disease Diseases 0.000 description 1
- 230000008558 metabolic pathway by substance Effects 0.000 description 1
- 238000002705 metabolomic analysis Methods 0.000 description 1
- 230000001431 metabolomic effect Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 150000002791 naphthoquinones Chemical class 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000032696 parturition Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 235000017924 poor diet Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 238000007781 pre-processing Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003761 preservation solution Substances 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 210000004994 reproductive system Anatomy 0.000 description 1
- 229960003471 retinol Drugs 0.000 description 1
- 235000020944 retinol Nutrition 0.000 description 1
- 239000011607 retinol Substances 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 208000004223 riboflavin deficiency Diseases 0.000 description 1
- 210000003786 sclera Anatomy 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 108010068815 steroid hormone 7-alpha-hydroxylase Proteins 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000001757 thermogravimetry curve Methods 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000021470 vitamin B5 (pantothenic acid) Nutrition 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000021467 vitamin B7(Biotin) Nutrition 0.000 description 1
- 235000019159 vitamin B9 Nutrition 0.000 description 1
- 239000011727 vitamin B9 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000005282 vitamin D3 Nutrition 0.000 description 1
- 239000011647 vitamin D3 Substances 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
- DIPPFEXMRDPFBK-JPWDPSJFSA-N vitamin D4 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CC[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C DIPPFEXMRDPFBK-JPWDPSJFSA-N 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 229940021056 vitamin d3 Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 235000021119 whey protein Nutrition 0.000 description 1
- 238000004383 yellowing Methods 0.000 description 1
- 239000008865 yin zhi huang Substances 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- 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
-
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/11—Lactobacillus
- A23V2400/143—Fermentum
-
- 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
- A23V2400/00—Lactic or propionic acid bacteria
- A23V2400/51—Bifidobacterium
- A23V2400/519—Breve
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Mycology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Epidemiology (AREA)
- Gastroenterology & Hepatology (AREA)
- Nutrition Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明提供了一种益生菌组合物和/或其代谢产物在制备治疗或辅助治疗黄疸或其相关疾病的产品上的用途,所述益生菌组合物含有双歧杆菌和乳杆菌。本发明提供的益生菌组合物可有效改善婴儿肠道的微生态环境,提高免疫力,并且还可以治疗光疗所造成的肠道损伤。
Description
技术领域
本发明属于生物制剂技术领域,尤其涉及一种益生菌组合物及其制备方法和用途。
技术背景
新生婴儿黄疸是因胆红素在体内积聚过多引起的皮肤或其他器官黄染,一般分为生理性黄疸和病理性黄疸。生理性黄疸是由新生婴儿的特殊生理特点引起的,临床表现为皮肤、眼球结膜发黄,一般在出生后2-3天内出现, 3-5天达到高峰期,足月婴儿黄疸一般在半个月内消退,早产婴儿可能延至一个月消退;病理性黄疸是由某种疾病引起的,临床表现为发病急,面部、颈部、四肢、躯干、巩膜呈黄色,严重者除了全身黄染,还伴有精神恍惚、恶心呕吐、饮食不振、舌苔薄白、尿液深黄、大便色淡如陶土等症状,持续时间长,两三周不消退,具有反复性。
新生婴儿黄疸发病率高,据统计,70%以上的新生婴儿会出现黄疸现象。目前国内外治疗黄疸的主要技术手段:(1)药物治疗,如酶诱导剂、糖皮质激素、中药(茵陈蒿汤、茵栀黄)等,(2)光疗,定时用蓝光照射,副作用较大,易引起发热、腹泻、皮疹、核黄素缺失、血小板减少、青铜症等。 (3)换血或输血,胆红素过高时也采用换血或输血,但供血者必须为非亲属,还需经过过筛试验,以免输血后加重病症,产生更多副作用,换血在技术上要求更高,临床应用受到局限。
发明内容
现有技术多为采用枯草杆菌二联活菌用于治疗或辅助治疗新生儿黄疸,鲜有报道关于采用双歧杆菌和乳杆菌用于治疗或辅助治疗新生儿黄疸及其相关疾病,本发明一申请目的在于提供一种双歧杆菌和乳杆菌组合物的新用途。
新生儿黄疸光疗后会对新生儿肠道产生损伤,本申请的另一目的在于提供一种双歧杆菌和乳杆菌组合物的另一新用途。
具体的方案如下:
一种益生菌组合物和/或其代谢产物在制备治疗或辅助治疗黄疸或其相关疾病的产品上的用途,所述益生菌组合物含有双歧杆菌和乳杆菌。
本申请所述治疗或辅助治疗也可以理解为改善,可以不是直接治疗。
本发明一具体实施方式,所述益生菌组合物含有所述益生菌组合物含有动物双歧杆菌、短双歧杆菌和发酵乳杆菌。
本发明一具体实施方式,所述产品选自药品或食品;所述益生菌组合物还包括一种或多种的食品上可接受的辅料或一种或多种的药学上可接受的辅料。
研究发现在新生儿黄疸数值高以后,经蓝光照射治疗,会造成体内的益生菌减少。而机体肠道内的菌群结构平衡、稳定和协调是婴幼儿健康的重要标志。它可以促进婴幼儿的生长发育;参与物质代谢、营养转化和合成;构成防止有害菌入侵的生物屏障;提高机体免疫力等。要使体内菌群处于正常水平,体外补充益生菌是措施之一。益生菌(Probiotics)是一类对宿主有益的活性微生物,是定植于人体肠道、生殖系统内,能产生确切健康功效从而改善宿主微生态平衡、发挥有益作用的活性有益微生物的总称。益生菌可通过减低婴儿肠道的通透性,提高肠道屏障功能和降解过敏物质,达到减少过敏物质吸收和刺激机体的作用。
申请人研究发现双歧杆菌对宿主的健康生存至关重要,它在机体内的有无或多寡是衡量健康状况的指标之一,直接或间接影响着人体的生理变化和免疫功能。双歧杆菌能产生乙酸、乳酸等有机酸降低肠道pH值和氧化还原点位,促进肠道蠕动,从而改善便秘,同时水解人体消化不完全的蛋白质,增加可溶性钙、铁及有些B族维生素的含量,起到营养补充作用。此外,它还能产生过氧化氢、细菌素等抗菌物质,抑制病原微生物的粘附生长,提高机体免疫力。
乳杆菌对肠道微生物有重要影响,它是兼性厌氧菌,主要分布在胃肠道的上半端,包括胃、回肠、结肠。通过对粪便中乳酸杆菌的计数分析鉴定发现,其数量超过1010CFU/g,包含嗜酸乳杆菌、唾液乳杆菌、干酪乳杆菌、植物乳杆菌、发酵乳杆菌、短乳杆菌等6个种。无论在食品发酵,还是在工业乳酸发酵以及医疗保健领域,乳杆菌都被广泛应用。
严格厌氧的双歧杆菌和兼性厌氧的乳杆菌在人体胃肠道的不同区域相辅相成,协同维持胃肠道健康。同一种属的菌种,即使菌株不同,其在稳定性、功效方面也有着天壤之别。
本发明提供了一种益生菌组合物和/或其代谢产物在制备治疗或辅助治疗黄疸光疗过程中造成的肠道损伤或其相关疾病的产品上的用途,所述益生菌组合物含有双歧杆菌和乳杆菌。
本发明一具体实施方式,所述益生菌组合物含有动物双歧杆菌、短双歧杆菌和发酵乳杆菌。
本发明一具体实施方式,所述产品选自药品或食品;所述益生菌组合物还包括一种或多种的食品上可接受的辅料或一种或多种的药学上可接受的辅料。
一种益生菌组合物,包括双歧杆菌和/或其代谢产物、乳杆菌和/或其代谢产物;进一步的还包括一种或多种的食品上可接受的辅料或一种或多种的药学上可接受的辅料;所述双歧杆菌选自动物双歧杆菌和短双歧杆菌,所述乳杆菌选自发酵乳杆菌。
本发明一具体实施方式,所述辅料选自脱盐乳清粉、脱脂奶粉、结构油脂、精炼植物油、α-乳白蛋白、麦芽糊精、乳糖、蔗果低聚糖、核苷酸、乳清蛋白肽、β-胡萝卜素、胆碱、L-肉碱、复合维生素、食用矿物、低聚半乳糖一种或多种。
本发明的组合物中,复合维生素可以选自由维生素A(视黄醇),维生素B1(硫胺),维生素B2(核黄素),维生素B3(烟酸),维生素B5(泛酸),维生素B6(吡哆辛),维生素B7(生物素),维生素B9(叶酸),维生素B12(氰钴胺),维生素C(抗坏血酸),维生素D(lamisterol),维生素D2(钙化醇),维生素D3(dihyrotachysterol),维生素D4(7- 去氢谷甾醇),维生素E(生育酚),和维生素K(萘醌)一种或多种的组合。食用矿物可以选自由钙氯化物,镁,磷,钾,钠,和硫所组成的组合物。
本发明一具体实施方式,所述组合物的制剂形式包括粉剂、颗粒剂、胶囊剂、片剂、滴剂、口服液。
一种益生菌组合物的制备方法,包括以下内容:将各组分按配比混合,或再辅以其他药学或食品中可接受的辅料或辅助性成分按照现有技术公开的工艺进行制备得到相应剂型的产品;若组分选用粉末制备成品,所述粉末组分包括制备成超微粉的组分。
本发明提供了益生菌组合物及其用途。该益生菌组合物包括双歧杆菌和乳杆菌,具体的是动物双歧杆菌、短双歧杆菌和发酵乳杆菌的组合。本发明中对包含该益生菌组合物的婴幼儿食品或药品进行了相关试验,试验结果表明该婴幼儿食品或药品能提高婴儿肠道中的相应益生菌含量,同时降低婴儿黄疸数值,有效改善婴儿黄疸病症,并且还能改善肠道的微生态环境。本发明所提供的益生菌组合物还具有治疗或辅助治疗因光疗造成的肠道损伤及肠道损伤相关的病症。
粪便中的双歧杆菌和乳杆菌的含量高,则肠道中双歧杆菌和乳杆菌数量多,其是衡量健康状况的指标之一,机体肠道中的有益菌可分解食物中的多糖,将其分解为乙酸、丙酸、丁酸等短链脂肪酸,因此粪便中的乙酸、丙酸、丁酸的含量及短链脂肪酸总含量可直接反应肠道中益生菌的数量,短链脂肪酸的含量高,则肠道中益生菌的数量多。
本发明的喂养或服用配方可以包含任何有效量,例如相应于约107至 1012cfu/g干重的量的益生菌。
本发明所述益生菌组合物不仅可以降低婴儿黄疸数值,同时还能改善婴儿的肠道微生态系统,增强抵抗力和改善代谢情况;特别的对经过光疗后的婴儿,还能修复因光疗造成的肠道损伤,尽快的重新建立或修复肠道的微生态系统。该组合物的服用还可以减少后期的神经和代谢方面的疾病,使得服用益生菌组合物具有一举多得的功效。
本申请通过宏基因测序和代谢组学的研究方法,阐明黄疸新生儿接受光疗治疗前后,肠道菌群中的益生菌株会发生显著改变,以及与其代谢指标的变化存在相关性。
附图说明
图1为光疗前后双歧杆菌的变化;
图2为光疗前后乳酸杆菌的变化;
图3为光疗后呈下降趋势的益生菌菌种间相关性对照;
图4为服用本发明益生菌制剂以后采集三个时间段的益生菌变化图;
图5为胆汁酸与益生菌间的相关性;
图6为代谢组学的试验数据,主要为胆汁酸的相关变化。
具体实施方式
下面将对本发明的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
除非另有定义,本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的,不是旨在于限制本发明。本文所使用的术语“及/或”包括一个或多个相关的所列项目的任意的和所有的组合。
本申请中,若无特殊申明所选用的原料、辅料均可通过市售购买得到。
黄疸新生儿最常规的治疗是光疗,光疗也报道有不同程度的副作用。但光疗过程中是否会造成其肠道菌群及其代谢的改变没有研究。
一、宏基因测序
1对象
1.1研究对象
1.1.1研究设计
选取2017年12月至2018年1月、2018年6月至2018年7月53例在上海市某儿科新生儿室、上海某大学附属儿科医院新生儿科需要光照治疗的足月新生儿为研究对象,采集患儿光疗前(BASELINE,简写为B)、光疗后 24小时(24H)、光疗后48小时(48H)的粪便样本,并按三个时间点将样本分成三组,总共收集159份粪便标本。
在家长完全自愿的情况下,我们给五位黄疸新生儿,光疗时添加我们的益生菌组合,同时也检测三个时间段的肠道菌群。
1.1.2入选标准
(1)37≤胎龄<42周;(2)日龄≤2周;(3)2500g≤出生体重≤4000g; (4)发生《实用新生儿学》定义的新生儿病理性黄疸,仅需要光照治疗的; (5)收集标本前均未使用微生态制剂及抗生素的;(6)母亲孕期身体健康,无特殊药物使用史,且产前、产时、产后均未服用微生态制剂及抗生素的; (7)所有患儿家属签署知情同意书。
2方法
2.1实验方法
DNA提取,DNA检测,文库构建,文库质检,上机测序,下机质控,信息分析。
2.1.1治疗方法
予入组患儿新生儿牛奶喂养、蓝光照射治疗。将患儿置于蓝光治疗箱(宁波戴维医疗器械公司,XHZ型号),设置箱内温度30℃,相对湿度55%,用波长425~475nm、双面LED蓝光持续式照射。
2.1.2标本采集与保存
(1)粪便的采集与保存:收集入组患儿B、24H、48H的粪便样本,从患儿尿不湿上采集新鲜粪便样本放入无菌冻存管,做好标记后立即用冰盒转运至实验室,冻存于-80℃冰箱,最后将所有收集到的粪便样本转运至北京的中国科学院微生物基因组学联合研究中心进行粪便DNA的提取及高通量测序。每例粪便样本≥500mg。
(2)胆红素的检测:经常规消毒后,在光疗前、光疗24小时抽取患儿静脉血2ml至采血管中,用AU2700全自动生化分析仪分析检测血清胆红素值。
2.1.3粪便样本DNA的提取
2.1.3.1实验步骤
(1)取1ml加有保存液的粪便样本到2ml Collection Tube中,13,000 x g离心10min进行富集;
(2)弃去上清,加入750ul PowerBead Solution,轻轻涡旋混匀;
(3)将混匀后的粪便样本转到Dry Bead Tube中;
(4)加入60ul C1溶液,上下颠倒数次或轻轻涡旋混匀;
(5)用多样品组织研磨机,以最大转速研磨2min;
(6)65℃水浴加热10min;
(7)13000x g离心1min;
(8)把上清液转移到干净的2ml Collection Tube中;
(9)加入250ul C2溶液,轻轻涡旋混匀,4℃孵育5min;
(10)13000x g离心1min;
(11)避免转移上清液时吸取到沉淀,转移不超过600ul上清到干净的 2mlCollection Tube中;
(12)加入200ul C3溶液,轻轻涡旋,4℃孵育5min;
(13)13000x g离心1min;
(14)避免转移上清液时吸取到沉淀,转移上清到一个干净的2ml CollectionTube中。转移的上清液不要超过750ul;
(15)加入1200ul C4溶液到上清中,涡旋5s混匀;
(16)将650ul上清液转移到MB Spin Column中,13000x g离心1min;弃去滤液,重复操作直至所有的上清液被转移;(一般需要转移3次上清)
(17)加入500ul C5溶液,13000x g离心1min;
(18)弃去滤液,13000x g再次离心2min;
(19)将MB Spin Column转移到干净的2ml Collection Tube中;
(20)加入60ul C6溶液到离心柱白色滤膜中心;
(21)13000x g离心1min,弃去Spin Filter basket,此时已完成 DNA的提取。(DNA建议-20℃~-80℃冷冻保存。)
2.1.4DNA样品检测
(1)Nanodrop测量DNA浓度:先用2ul去离子水清洗加样口,再用2ulC6 溶液做blank,取2ul DNA测量浓度。
(2)琼脂糖凝胶电泳检测DNA质量:上样体积为3ul,marker3ul,胶浓度1%,电压120V,跑胶需要45min左右。
2.1.5文库构建及质检
2.1.5.1实验步骤
S1DNA打断
A.Bioruptor插入片段在450bp左右
(1)将1.5~2ug细菌基因组DNA加入到bioruptor超声打断管里;
(2)用TE或RB缓冲液将总体积补充至80ul;
(3)仪器操作条件:high power、15’on/90’off、6cycles;
(4)片段化DNA检测:5ul片段化后的DNA产物;
(5)用1.5%的琼脂糖胶进行凝胶电泳(琼脂糖胶中加入1/10,000的染料),电泳条件:100V,40~60mins;检测DNA片段大小是否达到要求。注意:根据样本不同,打断条件可以进行微调。
B.用磁珠纯化
(1)取一新的1.5ml离心管,加入DNA体积0.8倍的磁珠(60ul),涡旋充分混匀,掌上离心机,短暂离心后,室温静置10分钟;
(2)将离心管放置磁珠架上,室温静置5分钟直至溶液变澄清;
(3)弃上清液,注意避免吸入磁珠;
(4)加200ul现配的80%乙醇溶液,室温静置30秒,弃乙醇溶液;(此步骤在磁珠架上操作)
(5)重复步骤4一次,完成两次乙醇清洗;
(6)短暂离心,把离心管壁上的溶液离心下来,用20微升移液器将剩下的溶液吸干净,注意避免吸入磁珠;
(7)室温晾干磁珠5分钟;注意尽量避免磁珠出现裂缝;
(8)加39ul RB,用移液器上下吹打溶液10次,使磁珠重新悬浮,室温静置2分钟;
(9)将离心管放置磁珠架上,室温静置5分钟直至溶液变得清亮;
(10)吸取37ul的上清液于PCR管中;
C.用nanodrop测纯化后产物浓度并记录
纯化后浓度应在10~30ng/ul,不符合的样本需要稀释或重新片段化。
S2末端补平&加A(全量)
(1)将5×ERA Buffer和ERA Enzyme Mix置于冰上融化,短暂混匀。
(2)反应体系
所有反应试剂加入PCR tube中,反应体系见下表1,100ul的移液器调整到50ul,用移液器上下吹打混合液10次,吹打过程中避免产生气泡。
表1末端补平&加A的反应体系各组分
成分 | 反应量(ul) |
DNA片段 | 37 |
5×ERA buffer | 10 |
ERA Enzyme Mix | 3 |
Total Volum | 50 |
(3)反应条件:
20℃下反应30分钟,2℃下反应30分钟,4℃后保温。
S3加接头
(1)反应体系
反应体系见下表2,200ul的移液器调整到100ul,上下吹打混合液10 次,注意避免产生气泡。注意:T4DNA Ligase比较粘稠,用移液器吸的时候要注意缓慢吸取。所有操作在4℃条件下(PCR仪上)进行。
表2加街头反应体系各组分
成分 | 反应量ul |
(二)中补平加A后的DNA | 50 |
T4Ligation Buffer | 42 |
T4DNA Ligase | 2 |
DNA Barcode(15uM) | 6 |
Total Volume | 100 |
(2)反应条件:
22℃下反应15分钟;PCR仪上面4℃保存半个小时以上。
S4磁珠选择DNA片段大小(以选择500~700bp为例)
(1)取一新的1.5ml离心管,向其中加入80ulAmp磁珠和100ul的连接产物,涡旋混匀,室温静置10min;
(2)将离心管置于磁力架上,静置5min,或至溶液澄清,去上清液;
(3)加入200ul 80%乙醇,静置30s,去上清液;
(4)重复(3)一次,完成2次乙醇清洗;
(5)短暂离心,把离心管壁上的溶液离心至管底,离心管放在磁力架上静置30秒,用移液器将剩下的溶液吸干净,注意避免吸入磁珠,室温静置5分钟,晾干磁珠;
(6)加入52ul的RB,混匀,室温静置2min,将离心管置于磁力架上,静置5min,使溶液变澄清;
(7)取一新的1.5ml离心管,向其中加入30ul磁珠(吸取磁珠时速度要慢一些,保证磁珠体积),取上述DNA的澄清液50ul于此离心管中,涡旋混匀,室温静置10min;
(8)将离心管置于磁力架上,静置5min,使溶液变澄清;
(9)取75ul澄清液放入新的1.5ml离心管中,加入10ul磁珠,涡旋混匀,静置10min,将离心管置于磁力架上,静置5min或至溶液变澄清,去澄清液;
(10)向离心管中加入200ul 80%乙醇,静置30s,去澄清液;
(11)重复10一次,完成2次乙醇清洗;
(12)短暂离心,把离心管壁上的溶液离心至管底,用移液器将剩下的溶液吸干净,注意避免吸入磁珠,室温静置5分钟,晾干磁珠(注意尽量不要让磁珠出现裂纹);
(13)将离心管从磁力架上取下,加入22ul RB,用移液枪反复吹打,至磁珠完全混匀,室温静置2min,将离心管置于磁力架上至溶液变澄清,取20ul上清液于一新的PCR管中。
S5PCR扩增
(1)反应体系
将反应试剂加入PCR小管中,反应体系见下表3,用移液器上下吹打混合液10次,吹打过程中避免产生气泡。
表3PCR扩增反应体系各组分
成分 | 反应量(ul) |
Ligated DNA | 20ul |
2X HiFi PCR Mix | 25ul |
PCR Primer Mix(PPM) | 5ul |
Total Volum | 50ul |
(2)PCR反应条件
98℃反应2min;98℃反应20sec,60℃反应30sec(重复98℃反应20sec,60 ℃反应30sec这个反应操作10-15次);72℃反应30sec;72℃反应5min;4 ℃后保温。
S6PCR产物纯化
(1)50ul PCR产物转移到加有40ul磁珠的1.5ml离心管中,涡旋混匀,静置10min;
(2)将离心管置于磁力架上,静置5min,或至溶液澄清,去上清液;
(3)加入200ul 80%乙醇,静置30s,去上清液;
(4)重复(3)一次,完成2次乙醇清洗;
(5)短暂离心,把离心管壁上的溶液离心至管底,离心管放在磁力架上静置30秒,用移液器将剩下的溶液吸干净,注意避免吸入磁珠,室温静置5分钟,晾干磁珠;
(6)加28ul RB,用移液枪反复吹打,至磁珠完全混匀,室温静置2分钟;
(7)将离心管放置磁珠架上,室温静置5分钟直至溶液变得清亮;
(8)用移液枪吸取26ul的上清液,转移至一个新的1.5ml离心管中;
(9)nanodrop测量文库浓度、电泳检测文库大小。
2.1.6上机测序
建库质检合格后,把不同文库按照有效浓度及目标下机数据量的需求混合后进行Illumina HiSeq测序。
2.2生物信息学分析
采用Illumina HiSeq测序平台测序获得的原始数据(Raw Data)存在一定比例的带接头的、重复的,以及测序质量很低的reads,这些reads会影响组装和后续分析,故需对下机的raw reads进行更严格的过滤,得到更高质量的clean reads,即测序数据预处理。
3实验结果
如图1、2,光疗前后,黄疸新生儿肠道菌群的益生菌菌株以及其代谢指标发生显著改变。在益生菌菌株的变化中,双歧杆菌和乳酸杆菌显著降低,乳酸杆菌的含量基础值偏低;在双歧杆菌的变化中,短双歧杆菌显著降低,长双歧杆菌和动物双歧杆菌也有降低;在乳酸杆菌中,发酵乳杆菌和延森乳酸菌降低显著。
通过separman秩相关性分析原理从双歧杆菌属、乳杆菌属向种水平分析随光疗时间变化的益生菌之间的相关性,呈正相关的表明两菌种之间具有协同作用,相关性主要发生在双歧杆菌之间,有统计学差异(P<0.05)的总共涉及13个菌种30个数据。本申请通过研究光疗对黄疸新生儿肠道益生菌改变的影响,得出在光疗过程中减少的肠道益生菌,从而合理选择益生菌辅助治疗新生儿黄疸,图3列出了双歧杆菌属、乳杆菌属在种水平上,平均相对丰度随光疗时间延长而下降的11个菌种间的相关性。
与短双歧杆菌有协同下降作用的检测到3个菌种,与长双歧杆菌有协同下降作用的检测到3个菌种,与动物双歧杆菌有协同下降作用的检测到1个菌种,与链状双歧杆菌有协同下降作用的检测到4个菌种,与假链状双歧杆菌有协同下降作用的检测到4个菌种,与齿双歧杆菌有协同下降作用的检测到1个菌种,与植物乳杆菌有协同下降作用的检测到3个菌种,与卷曲乳杆菌有协同下降作用的检测到1个菌种,差异具有统计学意义(P<0.05),未检测到与发酵乳杆菌、鼠李糖乳杆菌、淀粉乳杆菌、惰性乳杆菌有统计学差异的协同下降的益生菌菌种。综合来看,相关性主要集中在双歧杆菌菌种之间。
根据下降最显著,最有统计学意义的双歧杆菌的两种,和乳杆菌中的一种,如表4所示,作为我们的复合菌种的主要成分。
表4相关菌种的统计数据
最终选择动物双歧杆菌、短双歧杆菌和发酵乳杆菌的组合作为治疗或辅助治疗光疗造成的肠道损伤及相关病症。
本申请可选用的辅料包括脱盐乳清粉、脱脂奶粉、结构油脂、精炼植物油、α-乳白蛋白、麦芽糊精、乳糖、蔗果低聚糖、核苷酸、乳清蛋白肽、β-胡萝卜素、胆碱、L-肉碱、复合维生素、食用矿物、低聚半乳糖,可根据需要选择包括其中的一种或多种。
一具体的实施方式,选用低聚半乳糖作为辅料,并采用现有技术公开的制剂制备方法,将各组分制备成制成复合制剂,分别添加给五个黄疸新生儿,采集三个时间段的益生菌变化,结果如图4。
二、代谢组学关系
1、对象
宏基因测序中纳入研究的需要光照治疗的足月新生儿的粪便标本继续研究,分组同前文,采集不同光疗时间段,光疗前(BASELINE),光疗后 24小时(24H),光疗后48小时(48H),光疗治疗前后的黄疸新生儿大便,分离DNA通过宏基因测序检测光疗前后肠道益生菌菌株的变化,通过代谢组学方法检测黄疸新生儿大便在光疗前后代谢指标的变化。
2、结果
胆汁酸与益生菌间的相关性及差异分析:
从双歧杆菌属、乳杆菌属向种水平与胆汁酸行有差异的胆汁酸与益生菌的相关性
图5所示相关性热图显示,相关性主要表现在双歧杆菌与胆汁酸之间,在属水平,与双歧杆菌属呈正相关且有统计学意义的胆汁酸有5个,负相关的有4个,均为涉及DCA。与乳杆菌属呈负相关且有统计学意义的胆汁酸有2个,未测到有统计学意义的正相关性胆汁酸。与短双歧杆菌呈正相关且有统计学意义的胆汁酸有:6-ketoLCA、DCA、6,7-diketoLCA、GUCA、 GHDCA,未测到有统计学意义的负相关性胆汁酸。
胆汁酸是胆固醇代谢、脂质消化和人体其他调控途径的重要组成部分,作为胆汁的主要组成成分,在肠肝循环中发挥重要作用。饮食和肠道菌群与胆汁酸池相互作用,通过生物转化反应,影响胆汁酸的疏水性、毒性和调节作用。由疾病或临时的抗生素引起胆汁酸池的紊乱,可能导致多种疾病状态。胆固醇在肝内经7α-羟化酶的作用生成结合胆汁酸,排入肠道后的初级胆汁酸经过肠道菌群的早期解离、脱羟基作用、差异异构等的修饰作用下生成次级胆汁酸。在双歧杆菌、乳酸杆菌、拟杆菌等产生的胆盐水解酶(BSHs)的作用下,结合胆汁酸被水解为游离胆汁酸,再通过梭菌等的7α-脱羟基活性生成次级胆汁酸随粪便排出体外。可见,肠道菌群对胆汁酸的合成与代谢产生了重要影响。
补充双歧杆菌和乳杆菌时,粪便中的胆汁酸含量会显著下降。研究发现是益生菌抑制了肠道中梭菌属的生长,而梭菌属恰恰能够将初级胆汁酸转化为次级胆汁酸。本申请所述研究的差异分析结果显示,在光疗48H后,DCA 的含量升高,且与短双歧杆菌具有显著的相关性,差异具有统计学意义(P <0.05)。故可推测,黄疸患儿光疗后,肠道益生菌中的短双歧杆菌水平下降,减弱了它对肠道中梭菌生长的抑制作用,从而导致梭菌所具有的脱羟基作用加强,故次级胆汁酸DCA便生成增多。
在补充益生菌的代谢指标如图6,鹅去氧胆酸显著增高,可以提高处理胆红素的能力,经过补充后,从代谢指标帮助胆红素的排泄,如图6。
以上所述仅为本发明的优选实施例而已,并不用于限制本发明,对于本领域的技术人员来说,本发明可以有各种更改和变化。凡在本发明的精神和原则之内,所作的任何修改、等同替换、改进等,均应包含在本发明的保护范围之内。
Claims (10)
1.一种益生菌组合物和/或其代谢产物在制备治疗或辅助治疗黄疸或其相关疾病的产品上的用途,所述益生菌组合物含有双歧杆菌和乳杆菌。
2.根据权利要求1所述用途,其特征在于:所述益生菌组合物含有动物双歧杆菌、短双歧杆菌和发酵乳杆菌。
3.根据权利要求1所述用途,其特征在于:所述产品选自药品或食品;所述益生菌组合物还包括一种或多种的食品上可接受的辅料或一种或多种的药学上可接受的辅料。
4.一种益生菌组合物和/或其代谢产物在制备治疗或辅助治疗黄疸光疗过程中造成的肠道损伤或其相关疾病的产品上的用途,所述益生菌组合物含有双歧杆菌和乳杆菌。
5.根据权利要求4所述用途,其特征在于:所述益生菌组合物含有动物双歧杆菌、短双歧杆菌和发酵乳杆菌。
6.根据权利要求4所述用途,其特征在于:所述产品选自药品或食品;所述益生菌组合物还包括一种或多种的食品上可接受的辅料或一种或多种的药学上可接受的辅料。
7.一种益生菌组合物,其特征在于:包括动物双歧杆菌和/或其代谢产物,短双歧杆菌和/或其代谢产物,以及发酵乳杆菌和/或其代谢产物;进一步的还包括一种或多种的食品上可接受的辅料或一种或多种的药学上可接受的辅料。
8.根据权利要求7所述益生菌组合物,其特征在于:所述辅料选自脱盐乳清粉、脱脂奶粉、结构油脂、精炼植物油、α-乳白蛋白、麦芽糊精、乳糖、蔗果低聚糖、核苷酸、乳清蛋白肽、β-胡萝卜素、胆碱、L-肉碱、复合维生素、食用矿物、低聚半乳糖中一种或多种。
9.根据权利要求7所述益生菌组合物,其特征在于:所述组合物的制剂形式包括粉剂、颗粒剂、胶囊剂、片剂、滴剂、口服液。
10.如权利要求7-9任一所述益生菌组合物的制备方法,其特征在于,包括以下内容:将各组分按配比混合,即得。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010414426.7A CN111686134A (zh) | 2020-05-15 | 2020-05-15 | 一种益生菌组合物及其制备方法和用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202010414426.7A CN111686134A (zh) | 2020-05-15 | 2020-05-15 | 一种益生菌组合物及其制备方法和用途 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN111686134A true CN111686134A (zh) | 2020-09-22 |
Family
ID=72477847
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202010414426.7A Pending CN111686134A (zh) | 2020-05-15 | 2020-05-15 | 一种益生菌组合物及其制备方法和用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN111686134A (zh) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112870234A (zh) * | 2021-01-27 | 2021-06-01 | 四川九章生物科技有限公司 | 包含绿原酸的药物组合物在制备治疗病理性黄疸的药物中的用途 |
CN114158734A (zh) * | 2021-11-29 | 2022-03-11 | 内蒙古伊利实业集团股份有限公司 | 一种用于预防或改善黄疸的组合物及其应用 |
CN115068591A (zh) * | 2022-07-06 | 2022-09-20 | 合生元(广州)健康产品有限公司 | 一种包含骨桥蛋白的益生菌组合物 |
CN116135964A (zh) * | 2021-11-16 | 2023-05-19 | 锦乔生物科技有限公司 | 治疗或预防黄疸的乳酸菌组合物 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101496822A (zh) * | 2009-02-18 | 2009-08-05 | 上海谱莱生物技术有限公司 | 复合益生菌微生态制剂及制备方法 |
CN103053904A (zh) * | 2012-12-29 | 2013-04-24 | 北京中科邦尼国际科技有限责任公司 | 一种具有调节肠道菌群功能的复合功能糖 |
CN103637219A (zh) * | 2013-12-27 | 2014-03-19 | 浙江贝因美科工贸股份有限公司 | 益生菌组合物及其应用、婴幼儿食品 |
CN106038609A (zh) * | 2016-04-22 | 2016-10-26 | 深圳市儿童医院 | 拟杆菌在检测和治疗母乳性黄疸中的用途 |
CN110461337A (zh) * | 2017-02-23 | 2019-11-15 | 英特塞普特医药品公司 | 具有胆汁酸衍生物和微生物组的药物组合物及其用途 |
-
2020
- 2020-05-15 CN CN202010414426.7A patent/CN111686134A/zh active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101496822A (zh) * | 2009-02-18 | 2009-08-05 | 上海谱莱生物技术有限公司 | 复合益生菌微生态制剂及制备方法 |
CN103053904A (zh) * | 2012-12-29 | 2013-04-24 | 北京中科邦尼国际科技有限责任公司 | 一种具有调节肠道菌群功能的复合功能糖 |
CN103637219A (zh) * | 2013-12-27 | 2014-03-19 | 浙江贝因美科工贸股份有限公司 | 益生菌组合物及其应用、婴幼儿食品 |
CN106038609A (zh) * | 2016-04-22 | 2016-10-26 | 深圳市儿童医院 | 拟杆菌在检测和治疗母乳性黄疸中的用途 |
CN110461337A (zh) * | 2017-02-23 | 2019-11-15 | 英特塞普特医药品公司 | 具有胆汁酸衍生物和微生物组的药物组合物及其用途 |
Non-Patent Citations (3)
Title |
---|
FATMA SARAC ET AL.: "Effect of probiotic supplementation on bacterial translocation in common bile duct obstruction", 《PEDIATR SURG INT》, pages 155 - 161 * |
李松,晏咏梅: "双歧杆菌乳杆菌三联活菌治疗母乳性黄疸疗效观察", 《临床合理用药》, pages 74 * |
王微娜: "双歧杆菌乳杆菌三联活菌片联合蓝光照射治疗早产儿黄疸效果观察", 《中国乡村医药》, pages 22 - 23 * |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112870234A (zh) * | 2021-01-27 | 2021-06-01 | 四川九章生物科技有限公司 | 包含绿原酸的药物组合物在制备治疗病理性黄疸的药物中的用途 |
CN116135964A (zh) * | 2021-11-16 | 2023-05-19 | 锦乔生物科技有限公司 | 治疗或预防黄疸的乳酸菌组合物 |
CN116135964B (zh) * | 2021-11-16 | 2024-05-28 | 锦乔生物科技有限公司 | 治疗或预防黄疸的乳酸菌组合物 |
CN114158734A (zh) * | 2021-11-29 | 2022-03-11 | 内蒙古伊利实业集团股份有限公司 | 一种用于预防或改善黄疸的组合物及其应用 |
CN115068591A (zh) * | 2022-07-06 | 2022-09-20 | 合生元(广州)健康产品有限公司 | 一种包含骨桥蛋白的益生菌组合物 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN111686134A (zh) | 一种益生菌组合物及其制备方法和用途 | |
Wang et al. | Bifidobacteria exert species-specific effects on constipation in BALB/c mice | |
CN102657262B (zh) | 聚葡萄糖在配方奶喂养的婴儿体内模拟人乳低聚糖的功能属性的用途 | |
CN112175864B (zh) | 动物双歧杆菌及其选育方法和应用 | |
Vo et al. | Early exposure to agricultural soil accelerates the maturation of the early-life pig gut microbiota | |
EP2522358A1 (en) | Peptides against rotavirus infection | |
US11667977B2 (en) | Method of using a medication or a food supplement with lactobacillus strains isolated from kimere for strengthining the immune system | |
CN102399718B (zh) | 副干酪乳酸杆菌株gmnl‑133、用于改善异位性皮肤炎或其它过敏疾病的组合物及其用途 | |
Brudnak et al. | Enzyme-based therapy for autism spectrum disorders–is it worth another look? | |
CN1931879A (zh) | 银耳杂多糖或其提取物的新用途 | |
CN102274245A (zh) | 新颖乳杆菌及其组合物和在制备改善糖尿病及其并发症药物中的应用 | |
CN102935092A (zh) | 新颖乳杆菌及其组合物和在制备改善糖尿病及其并发症药物中的应用 | |
CN113215035A (zh) | 长双歧杆菌和动物双歧杆菌的制备及其在抗衰老方面的应用 | |
Lee et al. | Alleviating chronic kidney disease progression through modulating the critical genus of gut microbiota in a cisplatin-induced Lanyu pig model | |
Jagodzinski et al. | The early years of life. Are they influenced by our microbiome? | |
WO2018112739A1 (zh) | 一种假小链状双歧杆菌及其培养方法和应用 | |
CN115287224A (zh) | 一株改善本源动物肠道微生物发育的牦牛源罗伊氏乳杆菌及其应用 | |
CN116286551A (zh) | 长双歧杆菌婴儿亚种在调节体内脂肪代谢、塑形减脂改善肥胖方面的应用 | |
Niu et al. | Effect of fructooligosaccharides on the colonization of Lactobacillus rhamnosus AS 1.2466 T in the gut of mice | |
AboNahas et al. | Trust your gut: the human gut microbiome in health and disease | |
SULEIMAN et al. | Bacterial diarrhea among infants in developing countries: An overview of diarrheagenic Escherichia coli (DEC) | |
AU2016208007B2 (en) | A method of activating lactic acid bacteria | |
Mangwana | The in vitro faecal evaluation of prebiotic effects of rooibos phenolic compounds on the gut microbiota of vervet monkeys (Chlorocebus pygerythrus) | |
CN115068591B (zh) | 一种包含骨桥蛋白的益生菌组合物 | |
CN116391026A (zh) | 产生丝氨酸蛋白酶抑制剂 |
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 | ||
TA01 | Transfer of patent application right | ||
TA01 | Transfer of patent application right |
Effective date of registration: 20240320 Address after: No. 600 Yishan Road, Xuhui District, Shanghai, June 2013 Applicant after: SHANGHAI SIXTH PEOPLE'S Hospital Country or region after: Zhong Guo Address before: No. 222 Huanhu West Third Road, Nanhui New City, Pudong New Area, Shanghai, 200120 Applicant before: THE EAST HOSPITAL OF SHANGHAI THE SIXTH PEOPLES Hospital Country or region before: Zhong Guo |