CN116656549B - 一种能够改善睡眠质量的益生菌剂及其应用 - Google Patents
一种能够改善睡眠质量的益生菌剂及其应用 Download PDFInfo
- Publication number
- CN116656549B CN116656549B CN202310598410.XA CN202310598410A CN116656549B CN 116656549 B CN116656549 B CN 116656549B CN 202310598410 A CN202310598410 A CN 202310598410A CN 116656549 B CN116656549 B CN 116656549B
- Authority
- CN
- China
- Prior art keywords
- sleep quality
- probiotic
- strain
- mice
- improving
- 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
- 239000006041 probiotic Substances 0.000 title claims abstract description 79
- 235000018291 probiotics Nutrition 0.000 title claims abstract description 79
- 230000000529 probiotic effect Effects 0.000 title claims abstract description 57
- 230000003860 sleep quality Effects 0.000 title claims abstract description 34
- 241001134770 Bifidobacterium animalis Species 0.000 claims abstract description 12
- 229940118852 bifidobacterium animalis Drugs 0.000 claims abstract description 12
- 238000004321 preservation Methods 0.000 claims abstract description 11
- 244000199866 Lactobacillus casei Species 0.000 claims abstract description 9
- 241000901050 Bifidobacterium animalis subsp. lactis Species 0.000 claims abstract description 4
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 39
- 206010022437 insomnia Diseases 0.000 claims description 39
- 239000000843 powder Substances 0.000 claims description 25
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- UQZIYBXSHAGNOE-USOSMYMVSA-N Stachyose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](CO[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)[C@H](CO)O2)O1 UQZIYBXSHAGNOE-USOSMYMVSA-N 0.000 claims description 12
- UQZIYBXSHAGNOE-XNSRJBNMSA-N stachyose Chemical group O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO[C@@H]3[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O3)O)O2)O)O1 UQZIYBXSHAGNOE-XNSRJBNMSA-N 0.000 claims description 12
- WQZGKKKJIJFFOK-QTVWNMPRSA-N D-mannopyranose Chemical compound OC[C@H]1OC(O)[C@@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-QTVWNMPRSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 235000020183 skimmed milk Nutrition 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 230000002936 tranquilizing effect Effects 0.000 claims description 5
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 4
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 4
- 239000012752 auxiliary agent Substances 0.000 claims description 4
- 238000009472 formulation Methods 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- 239000002775 capsule Substances 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- 229920002307 Dextran Polymers 0.000 claims description 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 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 2
- 240000007472 Leucaena leucocephala Species 0.000 claims description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 239000008101 lactose Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000010413 sodium alginate Nutrition 0.000 claims description 2
- 239000000661 sodium alginate Substances 0.000 claims description 2
- 229940005550 sodium alginate Drugs 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 239000000811 xylitol Substances 0.000 claims description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 2
- 229960002675 xylitol Drugs 0.000 claims description 2
- 235000010447 xylitol Nutrition 0.000 claims description 2
- 230000000694 effects Effects 0.000 abstract description 19
- 150000001875 compounds Chemical class 0.000 abstract description 15
- 230000003993 interaction Effects 0.000 abstract description 4
- 230000002195 synergetic effect Effects 0.000 abstract 1
- 241000699670 Mus sp. Species 0.000 description 71
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 32
- 210000005013 brain tissue Anatomy 0.000 description 27
- 230000007958 sleep Effects 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- 210000004556 brain Anatomy 0.000 description 15
- 230000006870 function Effects 0.000 description 13
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 13
- 239000000243 solution Substances 0.000 description 13
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 12
- 229960001412 pentobarbital Drugs 0.000 description 12
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 12
- 239000000047 product Substances 0.000 description 11
- 230000001105 regulatory effect Effects 0.000 description 11
- 208000010340 Sleep Deprivation Diseases 0.000 description 10
- 230000002496 gastric effect Effects 0.000 description 10
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- 230000004620 sleep latency Effects 0.000 description 10
- 241001052560 Thallis Species 0.000 description 8
- 230000003542 behavioural effect Effects 0.000 description 8
- 230000000968 intestinal effect Effects 0.000 description 8
- 230000004065 mitochondrial dysfunction Effects 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 238000012360 testing method Methods 0.000 description 8
- 102000058063 Glucose Transporter Type 1 Human genes 0.000 description 7
- 108091006296 SLC2A1 Proteins 0.000 description 7
- 230000001580 bacterial effect Effects 0.000 description 7
- 239000002858 neurotransmitter agent Substances 0.000 description 7
- 208000019116 sleep disease Diseases 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- 235000013958 Lactobacillus casei Nutrition 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000008034 disappearance Effects 0.000 description 6
- 230000034659 glycolysis Effects 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 229940017800 lactobacillus casei Drugs 0.000 description 6
- 230000002035 prolonged effect Effects 0.000 description 6
- 238000012258 culturing Methods 0.000 description 5
- 239000004310 lactic acid Substances 0.000 description 5
- 235000014655 lactic acid Nutrition 0.000 description 5
- 239000008176 lyophilized powder Substances 0.000 description 5
- 230000004898 mitochondrial function Effects 0.000 description 5
- 229940076279 serotonin Drugs 0.000 description 5
- 230000004622 sleep time Effects 0.000 description 5
- 230000008454 sleep-wake cycle Effects 0.000 description 5
- 208000020685 sleep-wake disease Diseases 0.000 description 5
- 241000894006 Bacteria Species 0.000 description 4
- 101800000637 Hemokinin Proteins 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 4
- 241000186660 Lactobacillus Species 0.000 description 4
- 241000699666 Mus <mouse, genus> Species 0.000 description 4
- 102100023602 Protein Hook homolog 1 Human genes 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 230000037213 diet Effects 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 206010016256 fatigue Diseases 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 229940039696 lactobacillus Drugs 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000003470 mitochondria Anatomy 0.000 description 4
- 238000010172 mouse model Methods 0.000 description 4
- 239000008213 purified water Substances 0.000 description 4
- 230000004617 sleep duration Effects 0.000 description 4
- 230000009182 swimming Effects 0.000 description 4
- 238000012549 training Methods 0.000 description 4
- 102000018711 Facilitative Glucose Transport Proteins Human genes 0.000 description 3
- 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 3
- 108091052347 Glucose transporter family Proteins 0.000 description 3
- 208000006083 Hypokinesia Diseases 0.000 description 3
- 239000001888 Peptone Substances 0.000 description 3
- 108010080698 Peptones Proteins 0.000 description 3
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 235000015278 beef Nutrition 0.000 description 3
- KLOIYEQEVSIOOO-UHFFFAOYSA-N carbocromen Chemical compound CC1=C(CCN(CC)CC)C(=O)OC2=CC(OCC(=O)OCC)=CC=C21 KLOIYEQEVSIOOO-UHFFFAOYSA-N 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 235000013305 food Nutrition 0.000 description 3
- 238000007710 freezing Methods 0.000 description 3
- 230000008014 freezing Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 238000009629 microbiological culture Methods 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 230000002438 mitochondrial effect Effects 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000006872 mrs medium Substances 0.000 description 3
- 230000036542 oxidative stress Effects 0.000 description 3
- 235000019319 peptone Nutrition 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000036578 sleeping time Effects 0.000 description 3
- 239000002002 slurry Substances 0.000 description 3
- 239000001632 sodium acetate Substances 0.000 description 3
- 235000017281 sodium acetate Nutrition 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- QIJRTFXNRTXDIP-UHFFFAOYSA-N (1-carboxy-2-sulfanylethyl)azanium;chloride;hydrate Chemical compound O.Cl.SCC(N)C(O)=O QIJRTFXNRTXDIP-UHFFFAOYSA-N 0.000 description 2
- -1 5-HT and the like Chemical compound 0.000 description 2
- 229920002972 Acrylic fiber Polymers 0.000 description 2
- 102000007469 Actins Human genes 0.000 description 2
- 108010085238 Actins Proteins 0.000 description 2
- 208000019901 Anxiety disease Diseases 0.000 description 2
- 208000036649 Dysbacteriosis Diseases 0.000 description 2
- 208000027244 Dysbiosis Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 208000019914 Mental Fatigue Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 240000000103 Potentilla erecta Species 0.000 description 2
- 235000016551 Potentilla erecta Nutrition 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 230000037007 arousal Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 235000020279 black tea Nutrition 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 229960001305 cysteine hydrochloride Drugs 0.000 description 2
- 230000007140 dysbiosis Effects 0.000 description 2
- 230000001771 impaired effect Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 239000002054 inoculum Substances 0.000 description 2
- 238000009630 liquid culture Methods 0.000 description 2
- 230000006996 mental state Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000002068 microbial inoculum Substances 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000000803 paradoxical effect Effects 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 239000003642 reactive oxygen metabolite Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000011514 reflex Effects 0.000 description 2
- 235000021391 short chain fatty acids Nutrition 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 238000001262 western blot Methods 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- 230000002407 ATP formation Effects 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241001123946 Gaga Species 0.000 description 1
- 101000840551 Homo sapiens Hexokinase-2 Proteins 0.000 description 1
- 101001050577 Homo sapiens Kinesin-like protein KIF2A Proteins 0.000 description 1
- 101001026214 Homo sapiens Potassium voltage-gated channel subfamily A member 5 Proteins 0.000 description 1
- 101001048456 Homo sapiens Protein Hook homolog 2 Proteins 0.000 description 1
- 102100023426 Kinesin-like protein KIF2A Human genes 0.000 description 1
- 240000002262 Litsea cubeba Species 0.000 description 1
- 235000012854 Litsea cubeba Nutrition 0.000 description 1
- YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 239000002033 PVDF binder Substances 0.000 description 1
- 206010062519 Poor quality sleep Diseases 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 229960002433 cysteine Drugs 0.000 description 1
- 235000018417 cysteine Nutrition 0.000 description 1
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- UQLDLKMNUJERMK-UHFFFAOYSA-L di(octadecanoyloxy)lead Chemical compound [Pb+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O UQLDLKMNUJERMK-UHFFFAOYSA-L 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 229940045109 genistein Drugs 0.000 description 1
- TZBJGXHYKVUXJN-UHFFFAOYSA-N genistein Natural products C1=CC(O)=CC=C1C1=COC2=CC(O)=CC(O)=C2C1=O TZBJGXHYKVUXJN-UHFFFAOYSA-N 0.000 description 1
- 235000006539 genistein Nutrition 0.000 description 1
- ZCOLJUOHXJRHDI-CMWLGVBASA-N genistein 7-O-beta-D-glucoside Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=C2C(=O)C(C=3C=CC(O)=CC=3)=COC2=C1 ZCOLJUOHXJRHDI-CMWLGVBASA-N 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 229960003987 melatonin Drugs 0.000 description 1
- DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 1
- 235000013406 prebiotics Nutrition 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000013275 serotonin uptake Effects 0.000 description 1
- 150000004666 short chain fatty acids Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 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
-
- 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
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
- A61K9/1623—Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1658—Proteins, e.g. albumin, gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1664—Compounds of unknown constitution, e.g. material from plants or animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- 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
- C12N1/04—Preserving or maintaining viable microorganisms
-
- 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
-
- 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
- C12R2001/225—Lactobacillus
- C12R2001/245—Lactobacillus casei
-
- 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
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Mycology (AREA)
- Biomedical Technology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- General Chemical & Material Sciences (AREA)
- Neurology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Engineering & Computer Science (AREA)
- Virology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Anesthesiology (AREA)
- Botany (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明涉及一种能够改善睡眠质量的益生菌剂及其应用,所述能够改善睡眠质量的益生菌剂中的菌株包括保藏编号为CGMCC No.15410的动物双歧杆菌乳亚种Bifidobacterium animalis subsp.lactis BLa80菌株和保藏编号为CGMCCNo.24110的干酪乳杆菌Lactobacillus casei LC16菌株。本发明创造性地开发了一种全新的益生菌复配方式,发现两者存在潜在的相互作用,能够相互配合,在改善睡眠质量的功效上协同增效,与单一的BLa80菌株或单一的LC16菌株相比,两种菌的复配显著提高改善睡眠质量的功效。
Description
技术领域
本发明属于益生菌剂技术领域,涉及一种能够改善睡眠质量的益生菌剂及其应用,具体涉及一种能够改善睡眠质量的益生菌剂及其在制备镇静安神、提高睡眠质量的制剂中的应用、在制备预防或治疗失眠的药物中的应用、在制备改善脑组织线粒体功能障碍问题的产品中的应用。
背景技术
人的一生中约有1/3时间处于睡眠状态。睡眠是生物体的基本功能,对维持正常生理活动具有重要作用。高质量睡眠不仅有助于提高生活质量,而且在缓解疲劳、恢复体力、巩固记忆、维持代谢稳态等方面发挥着不可忽视的作用。研究表明,良好的睡眠可以降低某些慢性疾病的发病率,反之,睡眠不足则影响多种生理功能,例如认知、情绪、免疫、生殖功能等。
失眠被称为最常见的睡眠障碍和第二大精神障碍,其主要特征为睡眠质量、睡眠启动或睡眠维持不佳。大约有30%成年人受到睡眠障碍的困扰,其中6%~10%被诊断为失眠。研究表明睡眠障碍会对大脑组织线粒体造成影响。大脑具有较高的代谢率和能量需求,线粒体作为细胞产能的主要场所,大脑很大程度上依赖于线粒体功能。失眠将导致大脑组织线粒体结构损坏和功能障碍,短暂的睡眠时间会增加线粒体活性氧ROS产生、脂质过氧化作用及氧化应激反应相关的基因的表达,同时线粒体作为细胞氧化应激损伤的靶器官,可导致线粒体发生氧化应激损伤。另外,长期失眠会诱发多种疾病,同时,失眠也是抑郁症、躁郁症、焦虑症、糖尿病等多种疾病常见并发症。目前,化学药物是临床上治疗失眠的主要手段,但患者长期服用,容易造成一些神经损伤和依赖性,因此寻找一种高效、安全无毒副的失眠治疗方式迫在眉睫。
近年来大量研究表示,肠道菌群失调与睡眠障碍之间存在强相关性,靶向肠道菌群改善失眠的理论探索及应用热度逐渐上升。伴随着肠道菌群-脑轴的研究,肠道微生物被证明可能通过几种机制与大脑进行交流,通过产生功能性代谢产物,如五羟色胺5-HT、γ-氨基丁酸GABA、短链脂肪酸SCFAs等,其能作为脑神经递质,改善睡眠效率,减少神经元活动,调节心率,增强记忆和调节激素分泌;调节血清素系统,血清素,如5-HT等及其代谢产物褪黑素是生物体睡眠所必需的神经递质,而肠道是人体产生血清素最主要场所。肠道微生物的存在是肠道血清素合成的必要条件,更是调控外周-中枢血清素转运系统的关键因素。因此,使用益生菌控制肠道微生物群或许是一种有效的治疗或预防措施,可以改善睡眠障碍,安神助眠,缓解疲劳等神经疾病相关的问题,可作为一种调控肠脑轴的新作用靶点,并且是一种健康的治疗方案,具有广阔的市场应用前景。
因此,提供一种益生菌产品,用以改善睡眠、缓解疲劳乏力等神经疾病相关问题是目前亟待解决的技术问题。
发明内容
针对现有技术的不足,本发明的目的在于提供一种能够改善睡眠质量的益生菌剂及其应用,具体提供一种能够改善睡眠质量的益生菌剂及其在制备镇静安神、提高睡眠质量的制剂中的应用、在制备预防或治疗失眠的药物中的应用、在制备改善脑组织线粒体功能障碍问题的产品中的应用。
为达到此发明目的,本发明采用以下技术方案:
第一方面,本发明提供一种能够改善睡眠质量的益生菌剂,所述能够改善睡眠质量的益生菌剂中的菌株包括保藏编号为CGMCC No.15410的动物双歧杆菌乳亚种Bifidobacterium animalis subsp. lactisBLa80菌株和保藏编号为CGMCC No.24110的干酪乳杆菌Lactobacillus caseiLC16菌株。
本发明创造性地开发了一种全新的益生菌复配方式,将动物双歧杆菌乳亚种Bifidobacterium animalis subsp. lactisBLa80菌株和干酪乳杆菌Lactobacillus caseiLC16菌株进行复配,发现两者存在潜在的相互作用,能够相互配合,在改善睡眠质量的功效上协同增效,在使用菌量一致的情况下,与单一的BLa80菌株或单一的LC16菌株相比,两种菌的复配在上述功效的发挥显著提高,获得了本领域技术人员难以预见的技术效果。具体表现在:(1)显著延长睡眠时间,提高了睡眠质量,镇静安神;(2)参与调控脑神经递质5-HT、GABA和Glu,从而更加调节睡眠-觉醒周期动态平衡;(3)显著改善精神疲劳和乏力问题,改善行为活动和反应能力;(4)显著改善脑组织线粒体功能障碍问题。因此,该益生菌剂为改善睡眠质量提供了新的策略,其可以用于制备预防、缓解或治疗失眠的相关产品,具有广泛的应用前景。
由于动物双歧杆菌乳亚种Bifidobacterium animalis subsp. lactisBLa80菌株和干酪乳杆菌Lactobacillus caseiLC16菌株均为益生菌,因此其在用于制备预防、缓解或治疗失眠的相关产品时,安全性高,且不易产生抗药性。
优选地,所述动物双歧杆菌乳亚种Bifidobacterium animalis subsp. lactisBLa80菌株与干酪乳杆菌Lactobacillus caseiLC16菌株的活菌数之比为(3-5):1,例如3:1、7:2、4:1、9:2、5:1等,上述数值范围内的其他具体点值均可选择,在此便不再一一赘述。
基于BLa80菌株与LC16菌株的潜在相互作用关系,本发明还发现当两种菌株以上述特定的活菌数配比进行复合时,其在延长睡眠时间,提高睡眠质量,镇静安神,调节睡眠-觉醒周期动态平衡,改善行为活动和反应能力,改善脑组织线粒体功能障碍问题方面的功效更加显著。
优选地,所述益生菌剂的剂型包括冻干粉剂、胶囊剂、片剂或颗粒剂。
本发明所涉及的益生菌剂的剂型不受限制,包括最常用的冻干粉剂,或进一步制得的胶囊剂、片剂或颗粒剂。其中冻干粉剂示例性地可以采用如下方法制得:
将BLa80菌株与LC16菌株分别接种于培养基中进行培养,得到培养液;培养液离心,得到菌体;菌体用冻干保护剂重悬,得到重悬液;重悬液冻干,即得,然后按比例将二者复配。
优选地,所述培养基包括MRS培养基。
优选地,所述MRS培养基以浓度计包括:蛋白胨8-12 g/L、牛肉膏8-12 g/L、葡萄糖15-25 g/L、乙酸钠1-3 g/L、酵母粉3-7 g/L、柠檬酸氢二铵1-3 g/L、K2PO4·3H2O 2-3 g/L、MgSO4·7H2O 0.05-0.2 g/L、MnSO40.01-0.1 g/L、吐温80 0.5-2 mL/L、半胱氨酸盐酸盐0.1-1 g/L。
优选地,所述冻干采用真空冷冻法。
优选地,所述益生菌剂还含有功能助剂和冻干保护剂。
优选地,所述功能助剂包括水苏糖和/或低聚甘露糖,优选水苏糖和低聚甘露糖的组合。
优选地,所述水苏糖与低聚甘露糖的优选质量比为(2-4):1,例如2:1、5:2、3:1、7:2、4:1等,该数值范围内的其他具体点值均可选择,在此便不再一一赘述。
本发明还创造性地发现可在上述益生菌剂中加入水苏糖和/或低聚甘露糖作为功效助剂,进一步提高上述有益功效的发挥,当水苏糖和低聚甘露糖同时使用时功效更佳。
优选地,所述冻干保护剂包括脱脂乳、明胶、糊精、阿拉伯胶、右旋糖酐、藻胶钠、聚乙烯吡咯烷酮、蔗糖、乳糖、海藻糖、山梨醇或木糖醇中的任意一种或至少两种的组合。
第二方面,本发明提供根据第一方面所述的能够改善睡眠质量的益生菌剂在制备镇静安神、提高睡眠质量的制剂中的应用。
第三方面,本发明提供根据第一方面所述的能够改善睡眠质量的益生菌剂在制备预防或治疗失眠的药物中的应用。
第四方面,本发明提供根据第一方面所述的能够改善睡眠质量的益生菌剂在制备改善脑组织线粒体功能障碍问题的产品中的应用。
第五方面,本发明提供根据第一方面所述的能够改善睡眠质量的益生菌剂在制备调节睡眠-觉醒周期动态平衡的产品中的应用。
相对于现有技术,本发明具有以下有益效果:
本发明创造性地开发了一种全新的益生菌复配方式,将动物双歧杆菌乳亚种
Bifidobacterium animalis subsp. lactis
BLa80菌株和干酪乳杆菌
Lactobacillus casei
LC16菌株进行复配,发现两者存在潜在的相互作用,能够相互配合,在改善睡眠质量的功效上协同增效,在使用菌量一致的情况下,与单一的BLa80菌株或单一的LC16菌株相比,两种菌的复配在上述功效的发挥显著提高,获得了本领域技术人员难以预见的技术效果。具体表现在:(1)显著延长睡眠时间,提高了睡眠质量,镇静安神;(2)参与调控脑神经递质5-HT、GABA和Glu,从而更加调节睡眠-觉醒周期动态平衡;(3)显著改善精神疲劳和乏力问题,改善行为活动和反应能力;(4)显著改善脑组织线粒体功能障碍问题。因此,该益生菌剂为改善睡眠质量提供了新的策略,其可以用于制备预防、缓解或治疗失眠的相关产品,具有广泛的应用前景。
附图说明
图1是各组小鼠睡眠时间统计结果图;
图2是各组小鼠睡眠潜伏期统计结果图;
图3是各组小鼠脑组织中的5-HT水平统计结果图;
图4是各组小鼠脑组织中的GABA水平统计结果图;
图5是各组小鼠悬尾不动时间统计结果图;
图6是各组小鼠游泳时间统计结果图;
图7是各组小鼠脑组织中ATP浓度统计结果图;
图8是各组小鼠脑组织中乳酸浓度统计结果图;
图9是Western印迹检测脑组织兔抗己糖激酶HK1、HK2和葡萄糖转运蛋白GLUT1表达水平统计结果图;
图10是各组小鼠睡眠时间统计结果图;
图11是各组小鼠睡眠潜伏期统计结果图。
具体实施方式
下面通过具体实施方式来进一步说明本发明的技术方案。本领域技术人员应该明了,所述实施例仅仅是帮助理解本发明,不应视为对本发明的具体限制。
下述实施例中涉及的蛋白胨、牛肉膏、葡萄糖、乙酸钠、酵母粉、柠檬酸氢二铵、K2PO4·3H2O、MgSO4·7H2O、MnSO4、吐温80和半胱氨酸盐酸盐购自国药集团化学试剂有限公司。下述实施例中涉及的水苏糖为购自于承德京天食品科技有限公司的型号为P 70的产品;下述实施例中涉及的低聚甘露糖为购自于山东龙力生物科技有限公司的型号为P 95的产品。
下述实施例中涉及的培养基如下:
MRS培养基(g/L):蛋白胨10g/L、牛肉膏10g/L、葡萄糖20g/L、乙酸钠2g/L、酵母粉5g/L、柠檬酸氢二铵2g/L、K2PO4·3H2O 2.6g/L、MgSO4·7H2O 0.1g/L、MnSO40.05g/L、吐温801mL/L、半胱氨酸氨酸盐0.5g/L。
下述实施例所涉及的动物双歧杆菌乳亚种命名为动物双歧杆菌乳亚种Bifidobacterium animalis subsp. lactisBLa80菌株,保藏单位为中国微生物菌种保藏管理委员会普通微生物中心,保藏时间为2018年03月05日,保藏编号为CGMCC No.15410,地址为:北京市朝阳区北辰西路1号院3号。
下述实施例所涉及的干酪乳杆菌命名为干酪乳杆菌Lactobacillus caseiLC16菌株,保藏单位为中国微生物菌种保藏管理委员会普通微生物中心,保藏时间为2021年12月15日,保藏编号为CGMCC No.24110,地址为:北京市朝阳区北辰西路1号院3号。
下述实施例中涉及的BLa80冻干粉剂的制备:将BLa80菌株接种于脱脂乳中,37℃下培养20 h进行活化,得到活化液;将活化液按3%(v/v)的接种量接种于MRS液体培养基中,37℃下培养24 h,得到菌液;菌液离心得到菌体;将菌体与冻干保护剂(含有海藻糖100g/L、脱脂奶粉100g/L,溶剂为纯化水)混合重悬(冻干保护剂和菌体的质量比为2:1),得到重悬液;将重悬液采用真空冷冻法进行冻干,得到动物双歧杆菌乳亚种BLa80冻干粉,检测其活菌数超过5000亿CFU/g。
下述实施例中涉及的LC16冻干粉剂的制备:将LC16菌株接种于脱脂乳中,37℃下培养20 h进行活化,得到活化液;将活化液按3%(v/v)的接种量接种于MRS液体培养基中,37℃下培养24 h,得到菌液;菌液离心得到菌体;将菌体与冻干保护剂(含有海藻糖100g/L、脱脂奶粉100g/L,溶剂为纯化水)混合重悬(冻干保护剂和菌体的质量比为2:1),得到重悬液;将重悬液采用真空冷冻法进行冻干,得到干酪乳杆菌LC16冻干粉,检测其活菌数超过5000亿CFU/g。
实施例1
本实施例提供七种益生菌剂,分别如下:
(S1)上述制得的BLa80冻干粉剂;
(S2)上述制得的LC16冻干粉剂;
(S3)BLa80+ LC16复合菌剂,将制得的BLa80冻干粉剂与LC16冻干粉剂以活菌数4:1进行混合均匀即得;
(S4)BLa80+ ATCC393复合菌剂,将制得的BLa80冻干粉剂与ATCC393冻干粉剂以活菌数4:1进行混合均匀即得;
(S5)BLa80+LC16+水苏糖复合菌剂,将制得的BLa80冻干粉剂、LC16冻干粉剂与水苏糖进行混合,其中BLa80菌株与LC16菌株的活菌数为4:1,冻干菌粉总量与水苏糖的质量比为1:5;
(S6)BLa80+LC16+低聚甘露糖复合菌剂,将制得的BLa80冻干粉剂、LC16冻干粉剂与低聚甘露糖进行混合,其中BLa80菌株与LC16菌株的活菌数为4:1,冻干菌粉总量与低聚甘露糖的质量比为1:5;
(S7)BLa80+LC16+水苏糖+低聚甘露糖复合菌剂,将制得的BLa80冻干粉剂、LC16冻干粉剂、水苏糖、低聚甘露糖进行混合,其中BLa80菌株与LC16菌株的活菌数为4:1,冻干菌粉总质量与益生元总质量的比例为1:5,水苏糖与低聚甘露糖的质量比为3:1。
实施例2
本实施例探究本发明所涉及的益生菌剂(S1、S2、S3、S4)对失眠小鼠睡眠改善、脑神经递质5-HT和GABA含量、行为活动和反应能力、脑组织线粒体功能以及肠道菌群多样性的影响:
(1)动物分组和建立失眠小鼠模型:
所有小鼠(体重20±3g)均无特定病原体。健康雌性SPF级昆明种小鼠由上海实验动物中心提供,并给予小鼠常规颗粒状啮齿动物饮食和纯净水。所有涉及小鼠的程序均符合上海市实验动物护理与动物实验中心提供的指导原则(许可证号2022122002)。
总共48只小鼠(8只小鼠/组),随机挑取40只小鼠采用改良版水平转盘睡眠剥夺法构建失眠模型(参考:Suchecki D, Tufik S. Social stability attenuates the stressin the modified multiple platform method for paradoxical sleep deprivation inthe rat.Physiol Behav. 2000 Jan;68(3):309-16.)。使用亚克力塑料板构建一个长为110cm、宽为60cm、高为40cm的睡眠剥夺箱,以10cm纵向距离和13cm横向距离为标准,在其底部固定15个高为8cm、直径为6.5cm的圆柱形平台,注入23-25℃水至平台下1cm处,保持水温。待小鼠适应性培养7天后,对待造模小鼠进行站立训练,将其放置于圆柱平台上,当小鼠即将入睡时,由于肌肉松弛垂头触水或落入水中而惊醒,使其被迫保持清醒站立。在2周的造模期间,小鼠于早晚各休息1次,每次30min,每2天记录一次小鼠行为学改变,包括它们的精神状态、饮食等变化。
40只失眠模型小鼠随机等分为5组,分别为模型组、益生菌剂S1组(BLa80菌量为1×109 CFU/天)、益生菌剂S2组(LC16菌量为1×109 CFU/天)、益生菌剂S3组(BLa80和LC16总菌量为1×109 CFU/天)、益生菌剂S4组(BLa80和ATCC393总菌量为1×109 CFU/天)。剩余未经造模的8只小鼠作为对照组。站立训练第2周开始时进行灌胃给益生菌剂处理,每次益生菌剂溶于0.5 mL纯净水灌胃,正常对照组及模型组小鼠给予0.5 mL纯净水灌胃。末次(益生菌剂干预4周)灌胃给药12 h后,戊巴比妥钠过量麻醉处死小鼠。
(2)睡眠改善测试:参照文献(Zhao, W., Li, Y., Ma, W., Ge, Y., Huang, Y.,2015. A study on quality components and sleep-promoting effects of GABA blacktea. Food Funct. 6 (10), 3393–3398.),所有测试均在安静的环境中进行,于实验结束前一天进行测试,具体如下:
a. 戊巴比妥钠诱导睡眠持续时间试验:在睡眠测试中,睡眠和觉醒状态分别根据翻正反射是否消失来确定,翻正反射消失超过30s被认为表明睡眠。各组小鼠灌胃30 min后,对每只小鼠进行腹膜内给药戊巴比妥钠 (49 mg/kg.bw)。睡眠持续时间记录为从翻正反射消失到恢复的时间间隔。
结果如图1所示,由图可知,与CTL组相比,MC组小鼠睡眠时间显著缩短,即MC组小鼠出现了睡眠障碍,经过益生菌BLa80、LC16干预后,失眠小鼠的症状有所缓解,益生菌BLa80的效果更好;当复合菌干预时,失眠小鼠睡眠时间出现更加显著的延长(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
b. 戊巴比妥钠诱发睡眠潜伏期试验:给药干预30min,每只小鼠腹腔注射戊巴比妥钠,剂量为320 mg/kg.bw。睡眠潜伏期记录为从戊巴比妥钠注射到翻正反射消失的时间间隔。
结果如图2所示,由图可知,与CTL组相比,MC组失眠小鼠的睡眠潜伏期显著延长,但在益生菌BLa80、LC16干预后睡眠潜伏期有所改善,失眠小鼠更容易入睡,且复合菌干预的缓解程度更加显著,即失眠小鼠入睡障碍显著减轻(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
(3)脑内5-HT、GABA含量测定:小鼠处死后,立刻冰浴下开颅取全脑,在冰平皿上分离大脑,用冰0.9%氯化钠溶液冲洗血液,滤纸拭干,大脑称重后,加9倍量的冰0.9% NaCl溶液,4°C条件下匀浆,取浆液至2 mL离心管中4°C下3000r/min离心15min,取上清液,按照试剂盒(购于武汉纯度生物科技有限公司)说明书相关操作步骤测定5-HT和GAGA含量。
结果分别如图3和图4所示,由图可知,与CTL组比较,MC组小鼠脑组织中的5-HT和GABA水平显著降低,与MC组失眠小鼠相比,益生菌BLa80、LC16以及复合益生菌干预后,失眠小鼠的5-HT含量显著提高,益生菌BLa80和复合益生菌作用下,失眠小鼠的GABA含量显著升高。通常,大脑皮层细胞调控“兴奋”和“抑制”的平衡状态被打破就会导致失眠,睡眠觉醒与5-HT、GABA等神经递质密切相关,相互作用,共同维持睡眠觉醒。即该结果发现,益生菌复合组或许在调节睡眠-觉醒周期动态平衡方面能发挥较为显著的作用,减轻疲劳、缓解焦虑情绪。(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
(4)评估失眠小鼠行为活动和反应性:通过测量小鼠悬尾不动时间及游泳时间,于末次给益生菌剂30min后,测定小鼠5min内悬尾不动时间及游泳时间。
结果分别如图5和图6所示,由图可知,与CTL组比较,MC组小鼠悬尾不动时间显著延长、游泳时间显著缩短,但在益生菌干预作用下,各组小鼠的悬尾不动时间能显著缩短,且游泳时间也得到显著提高。即,该实验中益生菌的干预能改善失眠小鼠的行为能力和反应力(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
(5)生化检测脑组织中ATP、乳酸浓度:取各组小鼠脑组织样本,用冰0.9%氯化钠溶液冲洗血液,滤纸拭干,大脑称重后,加9倍量的冰0.9% NaCl溶液,4°C条件下匀浆,取浆液至2 mL离心管中4°C下3000r/min离心15min,取上清液,根据ATP及乳酸检测试剂盒(购于武汉纯度生物科技有限公司)说明书进行操作,测定其浓度。
结果分别如图7和图8所示,由图可知,与CTL组相比,MC组小鼠脑组织线粒体功能受到显著的损伤,线粒体结构损坏、功能障碍,失眠小鼠脑组织中ATP浓度降低,乳酸浓度增加。经益生菌BLa80、LC16以及复合组干预治疗后,脑组织线粒体功能有所修复,即ATP及乳酸浓度出现逆转,脑组织ATP浓度回升,乳酸浓度有所下降,且复合组的影响效果最显著(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
(6)Western印迹检测脑组织兔抗己糖激酶 (HK) 1、HK2和葡萄糖转运蛋白(GLUT) 1表达水平:取各组小鼠脑组织样本,将其剪成细小碎片,按10μL/mg量加入裂解液,至完全裂解,先测定上清液蛋白浓度,根据结果上样至SDS-PAGE凝胶,电泳分离蛋白后转膜至PVDF膜。使用5%脱脂牛奶于4°C低温环境中封闭过夜,加入1 :1 000稀释的HK1、HK2、GLUT1、β-actin 抗体,经几次室温孵育、PBST洗涤后,于暗室中加入ECL发光液进行反应后,在全自动化学发光分析仪中检测结果并读取灰度值,以β- actin为内参分析其灰度值。
结果如图9所示,由图可知,对比CTL组,MC组失眠小鼠脑组织中HK1、HK2和GLUT1表达显著升高。GLUT1及HK可用于衡量糖酵解水平,其中HK为糖酵解途径的关键限速酶之一,提高其活性可提高细胞糖酵解水平;GLUT1是哺乳动物细胞中分布最广的葡萄糖转运蛋白,GLUT1上调可有助于糖酵解速率和乳酸生成的增加,而糖酵解能力的提高也暗示着细胞线粒体功能障碍,糖酵解途径生成的乳酸含量越高,从而导致细胞呼吸过程中乳酸生成增多,ATP生成减少,最终导致脑组织线粒体功能损伤。在益生菌干预后,失眠小鼠脑组织中HK1、HK2和GLUT1表达下降,差异有统计学意义,且复合益生菌组效果最显著,即复合益生菌组对缓解失眠小鼠脑组织线粒体功能障碍的效果最佳。(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
实施例3
本实施例探究本发明所涉及的益生菌剂(S3、S5、S6、S7)对失眠小鼠睡眠改善的影响:
(1)动物分组和建立失眠小鼠模型:
所有小鼠(体重20±3g)均无特定病原体。健康雌性SPF级昆明种小鼠由上海实验动物中心提供,并给予小鼠常规颗粒状啮齿动物饮食和纯净水。所有涉及小鼠的程序均符合上海市实验动物护理与动物实验中心提供的指导原则(许可证号2022122002)。
总共48只小鼠(8只小鼠/组),随机挑取40只小鼠采用改良版水平转盘睡眠剥夺法构建失眠模型(参考:Suchecki D, Tufik S. Social stability attenuates the stressin the modified multiple platform method for paradoxical sleep deprivation inthe rat.Physiol Behav. 2000 Jan;68(3):309-16.)。使用亚克力塑料板构建一个长为110cm、宽为60cm、高为40cm的睡眠剥夺箱,以10cm纵向距离和13cm横向距离为标准,在其底部固定15个高为8cm、直径为6.5cm的圆柱形平台,注入23-25℃水至平台下1cm处,保持水温。待小鼠适应性培养7天后,对待造模小鼠进行站立训练,将其放置于圆柱平台上,当小鼠即将入睡时,由于肌肉松弛垂头触水或落入水中而惊醒,使其被迫保持清醒站立。在2周的造模期间,小鼠于早晚各休息1次,每次30min,每2天记录一次小鼠行为学改变,包括它们的精神状态、饮食等变化。
40只失眠模型小鼠随机等分为5组,分别为模型组、益生菌剂S3组(BLa80和LC16总菌量为1×109 CFU/天)、益生菌剂S5组(BLa80和LC16总菌量为1×109 CFU/天)、益生菌剂S6组(BLa80和LC16总菌量为1×109 CFU/天)、益生菌剂S7组(BLa80和LC16总菌量为1×109 CFU/天)。剩余未经造模的8只小鼠作为对照组。站立训练第2周开始时进行灌胃给益生菌剂处理,每次益生菌剂溶于0.5 mL纯净水灌胃,正常对照组及模型组小鼠给予0.5 mL纯净水灌胃。末次(益生菌剂干预4周)灌胃给药12 h后,戊巴比妥钠过量麻醉处死小鼠。
(2)睡眠改善测试:参照文献(Zhao, W., Li, Y., Ma, W., Ge, Y., Huang, Y.,2015. A study on quality components and sleep-promoting effects of GABA blacktea. Food Funct. 6 (10), 3393–3398.),所有测试均在安静的环境中进行,于实验结束前一天进行测试,具体如下:
a. 戊巴比妥钠诱导睡眠持续时间试验:在睡眠测试中,睡眠和觉醒状态分别根据翻正反射是否消失来确定,翻正反射消失超过30s被认为表明睡眠。各组小鼠灌胃30 min后,对每只小鼠进行腹膜内给药戊巴比妥钠 (49 mg/kg.bw)。睡眠持续时间记录为从翻正反射消失到恢复的时间间隔。
结果如图10所示,由图可知,经过益生菌剂干预后,失眠小鼠的症状有所缓解,且与S3相比,S5、S6、S7益生菌剂的效果更好,其中S7益生菌剂的效果最好(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
b. 戊巴比妥钠诱发睡眠潜伏期试验:给药干预30min,每只小鼠腹腔注射戊巴比妥钠,剂量为320 mg/kg.bw。睡眠潜伏期记录为从戊巴比妥钠注射到翻正反射消失的时间间隔。
结果如图11所示,由图可知,与CTL组相比,MC组失眠小鼠的睡眠潜伏期显著延长,但在益生菌剂干预后睡眠潜伏期有所改善,失眠小鼠更容易入睡,且与S3相比,S5、S6、S7益生菌剂的效果更好,其中S7益生菌剂的效果最好(图中数据使用R语言ggplot2函数进行统计分析,与模型组MC组相比,***代表p<0.0001,**代表p<0.001,*代表p<0.05)。
申请人声明,本发明通过上述实施例来说明本发明的一种能够改善睡眠质量的益生菌剂及其应用,但本发明并不局限于上述实施例,即不意味着本发明必须依赖上述实施例才能实施。所属技术领域的技术人员应该明了,对本发明的任何改进,对本发明产品各原料的等效替换及辅助成分的添加、具体方式的选择等,均落在本发明的保护范围和公开范围之内。
以上详细描述了本发明的优选实施方式,但是,本发明并不限于上述实施方式中的具体细节,在本发明的技术构思范围内,可以对本发明的技术方案进行多种简单变型,这些简单变型均属于本发明的保护范围。
另外需要说明的是,在上述具体实施方式中所描述的各个具体技术特征,在不矛盾的情况下,可以通过任何合适的方式进行组合,为了避免不必要的重复,本发明对各种可能的组合方式不再另行说明。
Claims (7)
1.一种能够改善睡眠质量的益生菌剂,其特征在于,所述能够改善睡眠质量的益生菌剂中的菌株为保藏编号为CGMCC No.15410的动物双歧杆菌乳亚种Bifidobacteriumanimalis subsp.lactis BLa80菌株和保藏编号为CGMCCNo.24110的干酪乳杆菌Lactobacillus casei LC16菌株;所述动物双歧杆菌乳亚种Bifidobacterium animalissubsp.lactis BLa80菌株与干酪乳杆菌Lactobacillus casei LC16菌株的活菌数之比为(3-5):1。
2.根据权利要求1所述的能够改善睡眠质量的益生菌剂,其特征在于,所述益生菌剂的剂型选自冻干粉剂、胶囊剂、片剂或颗粒剂。
3.根据权利要求1或2所述的能够改善睡眠质量的益生菌剂,其特征在于,所述益生菌剂还含有功能助剂和冻干保护剂;所述功能助剂为水苏糖和/或低聚甘露糖。
4.根据权利要求3所述的能够改善睡眠质量的益生菌剂,其特征在于,所述功能助剂为水苏糖和低聚甘露糖的组合。
5.根据权利要求3所述的能够改善睡眠质量的益生菌剂,其特征在于,所述冻干保护剂为脱脂乳、明胶、糊精、阿拉伯胶、右旋糖酐、藻胶钠、聚乙烯吡咯烷酮、蔗糖、乳糖、海藻糖、山梨醇或木糖醇中的任意一种或至少两种的组合。
6.根据权利要求1-5中任一项所述的能够改善睡眠质量的益生菌剂在制备镇静安神、提高睡眠质量的制剂中的应用。
7.根据权利要求1-5中任一项所述的能够改善睡眠质量的益生菌剂在制备预防或治疗失眠的药物中的应用。
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310598410.XA CN116656549B (zh) | 2023-05-25 | 2023-05-25 | 一种能够改善睡眠质量的益生菌剂及其应用 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN202310598410.XA CN116656549B (zh) | 2023-05-25 | 2023-05-25 | 一种能够改善睡眠质量的益生菌剂及其应用 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN116656549A CN116656549A (zh) | 2023-08-29 |
CN116656549B true CN116656549B (zh) | 2023-11-14 |
Family
ID=87711188
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202310598410.XA Active CN116656549B (zh) | 2023-05-25 | 2023-05-25 | 一种能够改善睡眠质量的益生菌剂及其应用 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN116656549B (zh) |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113430133A (zh) * | 2021-06-24 | 2021-09-24 | 微康益生菌(苏州)股份有限公司 | 一种能够缓解溃疡性结肠炎的复合益生菌、制备方法及其应用 |
CN114146100A (zh) * | 2021-11-22 | 2022-03-08 | 微康益生菌(苏州)股份有限公司 | 动物双歧杆菌乳亚种BLa80在制备抗轮状病毒感染致腹泻的药物或食物中的应用 |
CN114146101A (zh) * | 2021-11-22 | 2022-03-08 | 微康益生菌(苏州)股份有限公司 | 动物双歧杆菌乳亚种BLa80在制备调节肠道动力的药物或食物中的应用 |
CN114634901A (zh) * | 2022-05-18 | 2022-06-17 | 微康益生菌(苏州)股份有限公司 | 一种促进骨骼健康的干酪乳杆菌lc16及其培养方法与应用 |
CN114854643A (zh) * | 2022-06-02 | 2022-08-05 | 微康益生菌(苏州)股份有限公司 | 一种促进乳杆菌和双歧杆菌协同增殖的培养基及其应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
MY160376A (en) * | 2008-11-03 | 2017-03-15 | Nestec Sa | A nutritional composition comprising probiotics and improving sleep patterns |
US11331353B2 (en) * | 2014-03-25 | 2022-05-17 | Kabushiki Kaisha Yakult Honsha | Sleep quality improver |
-
2023
- 2023-05-25 CN CN202310598410.XA patent/CN116656549B/zh active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113430133A (zh) * | 2021-06-24 | 2021-09-24 | 微康益生菌(苏州)股份有限公司 | 一种能够缓解溃疡性结肠炎的复合益生菌、制备方法及其应用 |
CN114146100A (zh) * | 2021-11-22 | 2022-03-08 | 微康益生菌(苏州)股份有限公司 | 动物双歧杆菌乳亚种BLa80在制备抗轮状病毒感染致腹泻的药物或食物中的应用 |
CN114146101A (zh) * | 2021-11-22 | 2022-03-08 | 微康益生菌(苏州)股份有限公司 | 动物双歧杆菌乳亚种BLa80在制备调节肠道动力的药物或食物中的应用 |
CN114634901A (zh) * | 2022-05-18 | 2022-06-17 | 微康益生菌(苏州)股份有限公司 | 一种促进骨骼健康的干酪乳杆菌lc16及其培养方法与应用 |
CN114854643A (zh) * | 2022-06-02 | 2022-08-05 | 微康益生菌(苏州)股份有限公司 | 一种促进乳杆菌和双歧杆菌协同增殖的培养基及其应用 |
Non-Patent Citations (3)
Title |
---|
Effects of Probiotics on Cognitive Reactivity, Mood, and Sleep Quality;Angela Marotta 等;Frontiers in Psychiatry;1-11 * |
Improvements in sleep indices during exam stress due to consumption of a Bifidobacterium longum;Gerard M. Moloney, 等;Brain, Behavior, & Immunity - Health;第10卷;1-13 * |
具有降解胆固醇能力的益生菌菌株筛选;陈珂可;朱建国;姜甜;方曙光;;食品科技(第11期);12-16 * |
Also Published As
Publication number | Publication date |
---|---|
CN116656549A (zh) | 2023-08-29 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US5837238A (en) | Treatment of diarrhea | |
CN111728111A (zh) | 一种缓解焦虑或抑郁的益生菌组合物及其应用 | |
JP5392672B2 (ja) | 新規の乳酸桿菌株及びその使用 | |
CN111560331B (zh) | 一株副干酪乳杆菌及其应用 | |
EP3815702A1 (en) | Composition for promoting glucolipid metabolism, and preparation and application thereof | |
CN111297917A (zh) | 一种缓解急性酒精中毒的益生菌制剂及制备方法和应用 | |
US20210128649A1 (en) | Composition for promoting glucolipid metabolism, and preparation and application thereof | |
CN116211900B (zh) | 一种用于改善多囊卵巢综合征的微生态活菌制剂及其制备方法和应用 | |
CN114540245A (zh) | 一株同时具有缓解抑郁情绪及促进肠道分泌IgA功能的鼠李糖乳杆菌CCFM1228及其应用 | |
EP2821073B1 (en) | Agent for use in improving circadian rhythm sleep disorders | |
CN117887643B (zh) | 一种抗过敏的益生菌剂及其应用 | |
CN113969253B (zh) | 一株具有便秘治疗效果的乳双歧杆菌jybr-390及其应用和产品 | |
CN117778279A (zh) | 一种降解乙醇的益生菌剂及其应用 | |
CN113881597A (zh) | 一株能够提高吲哚丙烯酸以调节特异性IgE的罗伊氏乳杆菌 | |
CN116656549B (zh) | 一种能够改善睡眠质量的益生菌剂及其应用 | |
CN116509902B (zh) | 一种通过调节肠-脑轴改善由环境污染引起的精神类疾病的益生菌剂及其应用 | |
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 | |
CN113913330B (zh) | 一株调节OVA特异性IgE的植物乳杆菌及其应用 | |
CN117887646B (zh) | 一种抗焦虑和抑郁的复合益生菌及其应用 | |
CN117987333B (zh) | 一种缓解运动疲劳的复合益生菌及其应用 | |
CN118406622A (zh) | 一种改善抑郁或焦虑的益生菌剂及其应用 | |
CN114657110B (zh) | 一种发酵乳杆菌iob802及其改善睡眠障碍的用途 | |
CN118086152B (zh) | 一种改善细菌性阴道炎的复合益生菌、益生菌剂及其应用 | |
US20230414685A1 (en) | Lactobacillus plantarum pda6 having neurological effects and compositions including the same | |
CN112914107B (zh) | 一株用于治疗抑郁的益生菌株Ls17及其应用 |
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 |