CN106256352A - 用于减少与pm2.5暴露相关的肺部和/或全身性炎症的组合物及其用途 - Google Patents
用于减少与pm2.5暴露相关的肺部和/或全身性炎症的组合物及其用途 Download PDFInfo
- Publication number
- CN106256352A CN106256352A CN201610695981.5A CN201610695981A CN106256352A CN 106256352 A CN106256352 A CN 106256352A CN 201610695981 A CN201610695981 A CN 201610695981A CN 106256352 A CN106256352 A CN 106256352A
- Authority
- CN
- China
- Prior art keywords
- compositions
- vitamin
- group
- systemic inflammatory
- relevant
- 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
- 239000000203 mixture Substances 0.000 title claims abstract description 44
- 230000002757 inflammatory effect Effects 0.000 title claims abstract description 26
- 230000002685 pulmonary effect Effects 0.000 title claims abstract description 22
- 230000009885 systemic effect Effects 0.000 title claims abstract description 22
- 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 claims abstract description 41
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims abstract description 40
- 239000006041 probiotic Substances 0.000 claims abstract description 25
- 235000018291 probiotics Nutrition 0.000 claims abstract description 25
- 230000000529 probiotic effect Effects 0.000 claims abstract description 24
- DVSZKTAMJJTWFG-UHFFFAOYSA-N docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCCC=CC=CC=CC=CC=CC=CC(O)=O DVSZKTAMJJTWFG-UHFFFAOYSA-N 0.000 claims abstract description 23
- MBMBGCFOFBJSGT-KUBAVDMBSA-N docosahexaenoic acid Natural products CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCC(O)=O MBMBGCFOFBJSGT-KUBAVDMBSA-N 0.000 claims abstract description 23
- 229930003427 Vitamin E Natural products 0.000 claims abstract description 20
- 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 claims abstract description 20
- 235000019165 vitamin E Nutrition 0.000 claims abstract description 20
- 239000011709 vitamin E Substances 0.000 claims abstract description 20
- 229940046009 vitamin E Drugs 0.000 claims abstract description 20
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229930003268 Vitamin C Natural products 0.000 claims abstract description 19
- 235000019154 vitamin C Nutrition 0.000 claims abstract description 19
- 239000011718 vitamin C Substances 0.000 claims abstract description 19
- 241001134770 Bifidobacterium animalis Species 0.000 claims abstract description 15
- 230000000172 allergic effect Effects 0.000 claims abstract description 5
- 208000024891 symptom Diseases 0.000 claims abstract description 4
- 208000010668 atopic eczema Diseases 0.000 claims abstract 3
- 210000004072 lung Anatomy 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 22
- 235000013305 food Nutrition 0.000 claims description 19
- 239000003344 environmental pollutant Substances 0.000 claims description 16
- 231100000719 pollutant Toxicity 0.000 claims description 16
- 235000015097 nutrients Nutrition 0.000 claims description 15
- 239000013589 supplement Substances 0.000 claims description 11
- 239000000843 powder Substances 0.000 claims description 10
- 229940112822 chewing gum Drugs 0.000 claims description 8
- 235000015218 chewing gum Nutrition 0.000 claims description 8
- 239000002775 capsule Substances 0.000 claims description 7
- 239000003826 tablet Substances 0.000 claims description 7
- 235000013361 beverage Nutrition 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 241000894006 Bacteria Species 0.000 claims description 5
- 241000186016 Bifidobacterium bifidum Species 0.000 claims description 5
- 239000002537 cosmetic Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 229940118852 bifidobacterium animalis Drugs 0.000 claims description 4
- 241000196324 Embryophyta Species 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 239000007894 caplet 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
- 235000009508 confectionery Nutrition 0.000 claims description 2
- 235000014510 cooky Nutrition 0.000 claims description 2
- 235000011869 dried fruits Nutrition 0.000 claims description 2
- 235000015203 fruit juice Nutrition 0.000 claims description 2
- 235000015243 ice cream Nutrition 0.000 claims description 2
- 150000008442 polyphenolic compounds Chemical class 0.000 claims description 2
- 235000013824 polyphenols Nutrition 0.000 claims description 2
- 235000013311 vegetables Nutrition 0.000 claims description 2
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 235000007688 Lycopersicon esculentum Nutrition 0.000 claims 1
- 240000003768 Solanum lycopersicum Species 0.000 claims 1
- 229910052799 carbon Inorganic materials 0.000 claims 1
- 235000020510 functional beverage Nutrition 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- 239000012676 herbal extract Substances 0.000 claims 1
- 238000003915 air pollution Methods 0.000 abstract description 15
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 7
- 108090000978 Interleukin-4 Proteins 0.000 abstract description 6
- 206010035664 Pneumonia Diseases 0.000 abstract description 6
- 239000000090 biomarker Substances 0.000 abstract description 2
- 238000010231 histologic analysis Methods 0.000 abstract description 2
- 230000001502 supplementing effect Effects 0.000 abstract 1
- 230000004054 inflammatory process Effects 0.000 description 20
- 102000004127 Cytokines Human genes 0.000 description 18
- 108090000695 Cytokines Proteins 0.000 description 18
- 206010061218 Inflammation Diseases 0.000 description 18
- 230000014509 gene expression Effects 0.000 description 15
- 235000005911 diet Nutrition 0.000 description 14
- 230000037213 diet Effects 0.000 description 14
- 241000699670 Mus sp. Species 0.000 description 13
- 230000008569 process Effects 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 108090000174 Interleukin-10 Proteins 0.000 description 9
- 108090000623 proteins and genes Proteins 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 102000011690 Adiponectin Human genes 0.000 description 8
- 108010076365 Adiponectin Proteins 0.000 description 8
- 208000006673 asthma Diseases 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 239000005482 chemotactic factor Substances 0.000 description 8
- 210000004027 cell Anatomy 0.000 description 7
- 230000036542 oxidative stress Effects 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 6
- 230000000770 proinflammatory effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 241000901050 Bifidobacterium animalis subsp. lactis Species 0.000 description 5
- 208000037883 airway inflammation Diseases 0.000 description 5
- 238000011160 research Methods 0.000 description 5
- 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 5
- 101100152731 Arabidopsis thaliana TH2 gene Proteins 0.000 description 4
- 102100032366 C-C motif chemokine 7 Human genes 0.000 description 4
- 101000897480 Homo sapiens C-C motif chemokine 2 Proteins 0.000 description 4
- 206010020751 Hypersensitivity Diseases 0.000 description 4
- 101150002020 Il23a gene Proteins 0.000 description 4
- 108010002616 Interleukin-5 Proteins 0.000 description 4
- 208000026935 allergic disease Diseases 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000003963 antioxidant agent Substances 0.000 description 4
- 230000003078 antioxidant effect Effects 0.000 description 4
- 235000006708 antioxidants Nutrition 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 3
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 3
- 101150009911 Ccl7 gene Proteins 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- 206010057190 Respiratory tract infections Diseases 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 210000001552 airway epithelial cell Anatomy 0.000 description 3
- 230000007815 allergy Effects 0.000 description 3
- 230000003064 anti-oxidating effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 208000037976 chronic inflammation Diseases 0.000 description 3
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 3
- 230000002079 cooperative effect Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 230000002327 eosinophilic effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- 230000003448 neutrophilic effect Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- -1 such as Substances 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 206010002198 Anaphylactic reaction Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000186000 Bifidobacterium Species 0.000 description 2
- 101150075117 Ccl12 gene Proteins 0.000 description 2
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 101000797758 Homo sapiens C-C motif chemokine 7 Proteins 0.000 description 2
- 108010065637 Interleukin-23 Proteins 0.000 description 2
- 102000013264 Interleukin-23 Human genes 0.000 description 2
- 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- 241000186660 Lactobacillus Species 0.000 description 2
- 208000019693 Lung disease Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- 210000004241 Th2 cell Anatomy 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 208000037884 allergic airway inflammation Diseases 0.000 description 2
- 230000009285 allergic inflammation Effects 0.000 description 2
- 201000010105 allergic rhinitis Diseases 0.000 description 2
- 229940087168 alpha tocopherol Drugs 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 208000003455 anaphylaxis Diseases 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 229940009289 bifidobacterium lactis Drugs 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003245 coal Substances 0.000 description 2
- 235000020940 control diet Nutrition 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 238000000855 fermentation Methods 0.000 description 2
- 230000004151 fermentation Effects 0.000 description 2
- 210000000630 fibrocyte Anatomy 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 230000000984 immunochemical effect Effects 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 229940039696 lactobacillus Drugs 0.000 description 2
- 230000002045 lasting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 230000035764 nutrition Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 2
- 229940012843 omega-3 fatty acid Drugs 0.000 description 2
- 230000003647 oxidation Effects 0.000 description 2
- 238000007254 oxidation reaction Methods 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000009469 supplementation Effects 0.000 description 2
- 229960000984 tocofersolan Drugs 0.000 description 2
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 2
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- 239000002076 α-tocopherol Substances 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- 102000003808 Adiponectin Receptors Human genes 0.000 description 1
- 108090000179 Adiponectin Receptors Proteins 0.000 description 1
- 238000011725 BALB/c mouse Methods 0.000 description 1
- 241000193830 Bacillus <bacterium> Species 0.000 description 1
- 101001042337 Burkholderia plantarii Lipase-specific foldase Proteins 0.000 description 1
- 101710155834 C-C motif chemokine 7 Proteins 0.000 description 1
- 102000001902 CC Chemokines Human genes 0.000 description 1
- 108010040471 CC Chemokines Proteins 0.000 description 1
- 101150052909 CCL2 gene Proteins 0.000 description 1
- 101150102665 CCL20 gene Proteins 0.000 description 1
- 101150093802 CXCL1 gene Proteins 0.000 description 1
- 101150077124 CXCL10 gene Proteins 0.000 description 1
- 108010055124 Chemokine CCL7 Proteins 0.000 description 1
- 208000028399 Critical Illness Diseases 0.000 description 1
- 101150097262 Cxcl5 gene Proteins 0.000 description 1
- 241000239366 Euphausiacea Species 0.000 description 1
- 241000167880 Hirundinidae Species 0.000 description 1
- 101150085950 IL10 gene Proteins 0.000 description 1
- 101150083678 IL2 gene Proteins 0.000 description 1
- 101150081923 IL4 gene Proteins 0.000 description 1
- 101150015560 IL5 gene Proteins 0.000 description 1
- 201000009794 Idiopathic Pulmonary Fibrosis Diseases 0.000 description 1
- 101150029237 Il11 gene Proteins 0.000 description 1
- 101150098378 Il17a gene Proteins 0.000 description 1
- 101150106555 Il24 gene Proteins 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 102100037850 Interferon gamma Human genes 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000013462 Interleukin-12 Human genes 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 108010064136 Monocyte Chemoattractant Proteins Proteins 0.000 description 1
- 102000014962 Monocyte Chemoattractant Proteins Human genes 0.000 description 1
- 241000699729 Muridae Species 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 101100165560 Mus musculus Bmp7 gene Proteins 0.000 description 1
- 101100382870 Mus musculus Ccl12 gene Proteins 0.000 description 1
- 101100166829 Mus musculus Cenpk gene Proteins 0.000 description 1
- 101100072418 Mus musculus Il22 gene Proteins 0.000 description 1
- 101100369993 Mus musculus Tnfsf10 gene Proteins 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 108010070519 PAR-1 Receptor Proteins 0.000 description 1
- 102000032626 PAR-1 Receptor Human genes 0.000 description 1
- 241000235070 Saccharomyces Species 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 101150073743 TNFRSF11B gene Proteins 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000809 air pollutant Substances 0.000 description 1
- 231100001243 air pollutant Toxicity 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 210000001132 alveolar macrophage Anatomy 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000008277 atmospheric particulate matter Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000000941 bile Anatomy 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000003399 chemotactic effect Effects 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- CYQFCXCEBYINGO-IAGOWNOFSA-N delta1-THC Chemical compound C1=C(C)CC[C@H]2C(C)(C)OC3=CC(CCCCC)=CC(O)=C3[C@@H]21 CYQFCXCEBYINGO-IAGOWNOFSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- GLCGEJFIZRSXBL-UHFFFAOYSA-N dodeca-1,3,5,7,9,11-hexaene Chemical compound C=CC=CC=CC=CC=CC=C GLCGEJFIZRSXBL-UHFFFAOYSA-N 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 210000000222 eosinocyte Anatomy 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 230000003054 hormonal effect Effects 0.000 description 1
- 102000046768 human CCL2 Human genes 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 208000036971 interstitial lung disease 2 Diseases 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000029052 metamorphosis Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000011236 particulate material Substances 0.000 description 1
- 239000013618 particulate matter Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 231100000255 pathogenic effect Toxicity 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000003334 potential effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 208000005069 pulmonary fibrosis Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 210000005181 root of the tongue Anatomy 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
Classifications
-
- 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
-
- 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
-
- 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
- A23L33/115—Fatty acids or derivatives thereof; Fats or oils
- A23L33/12—Fatty acids or derivatives thereof
-
- 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
- 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
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
- A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/36—Carboxylic acids; Salts or anhydrides thereof
- A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/678—Tocopherol, i.e. vitamin E
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P39/00—General protective or antinoxious agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/10—General cosmetic use
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Polymers & Plastics (AREA)
- Food Science & Technology (AREA)
- Nutrition Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Birds (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Immunology (AREA)
- Molecular Biology (AREA)
- Dermatology (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Toxicology (AREA)
- Emergency Medicine (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了一种用于减少与PM2.5暴露相关的肺部和/或全身性炎症的组合物,其包含二十二碳六烯酸、益生菌株(如动物双歧杆菌乳双歧杆菌亚种)、维生素C和维生素E。如补充前后的组织学分析测量的,所述组合物有助于减少与空气污染相关的肺部炎症。组合物还可以通过控制TH‑2抗炎生物标记物,如白介素‑4(IL‑4)和IL‑10的水平,帮助降低与全身性炎症关联的空气污染相关的过敏症状。特别地,该组合物可用于生活在PM2.5日平均水平为25至500μg/m3,特别是100至500μg/m3的环境中的人受试者。
Description
技术领域
本发明涉及一种用于减少由空气污染,特别是高水平的PM2.5污染物导致的肺部和/或全身性炎症的营养组合物及其用途。本发明还涉及用于减少与PM2.5暴露相关的肺部和/或全身性炎症的方法。
背景技术
在工业化国家和发展中国家中,哮喘、过敏性鼻炎和特应性皮炎的发生在最近的四十年间中不断增加。许多研究指出各种环境因素,如加快的工业化、饮食变化和空气污染对这些过敏性和炎症疾病的增多起着潜在的作用(Rutkowski等人,Allergic diseases:the price of civilisational progress,Postep Derm Allergol 2014;XXXI,2:77-83)。
中国和其他快速发展的国家的情况尤为令人担忧,在这些国家中,迅速发展的经济导致危害健康的污染水平的形成。在主要的污染物中,PM2.5,即空气动力学直径小于2.5微米的颗粒物质的水平必须考虑在内,因为它们可以携带有毒物质进而被吸入肺部。目前,北京的日平均PM2.5水平为2005年WHO准则规定的最大安全水平—25μg/m3的5倍,测得的峰值甚至为其20倍(WHO,2005,参见:http://www.who.int/phe/health_topics/outdoorair/outdoorair_aqg/en/)。高水平的PM2.5与一些健康问题有关,其中包括局部或全身炎症反应增加,以及抗氧化能力下降,导致细胞损伤和死亡。
尽管采取了长期持续的方法来减少PM2.5的排放,但是补充特定的营养物可以有助于预防或至少延缓与空气污染相关的炎症的发生,特别是对于具有较大风险的人群,如婴儿和儿童。
维生素E和维生素C具有熟知的抗氧化特性。最近的研究表明补充维生素E和维生素C可以帮助减少与高PM2.5水平相关的氧化应激和鼻部炎症,但是效果并不能持久(Possamai等人,Antioxidant intervention compensates oxidative stress in bloodof subjects exposed to emissions from a coal electric-power plant in SouthBrazil,Environ Toxicol Pharmacol.2010Sep;30(2):175-80;Sienra-Monge等人,Antioxidant supplementation and nasal inflammatory responses among youngasthmatics exposed to high levels of ozone,Clin.Exp.Immunol.2004Nov;138(2):317-22)。
很久之前就已经认识到Ω-3脂肪酸的抗炎和抗氧化作用。有个别报道表明鱼油(包含DHA-二十二碳六烯酸)在减少氧化应激和改善心率变异性中的作用(Zhang W.等人.Nutrition Solutions to Counter Health Impact of Air Pollution:ScientificEvidence of Marine Omega-3Fatty Acids and Vitamins Minimizing Some Harms ofPM2.5,J.Food NutrSci,2015,2(2):1-6)。
有一些相关的科学研究证明某些益生菌可以帮助恢复肠道菌群的适当的平衡,以及改善胃肠道症状。而且,有关免疫功能的临床研究显示特定的细菌,如益生菌株—动物双歧杆菌乳双歧杆菌亚种(Bifidobacterium animalis subsp.Lactis)提高了人体对常见呼吸道感染的抵抗力以及降低了急性呼吸道感染的发病(Jungersen等人,The Sciencebehind the Probiotic Strain Bifidobacterium animalis subsp.lactis BB-Microorganisms,2014,2,92-110;Mortaz等人,Probiotics in the Management of LungDiseases,Mediators of Inflammation,vol.2013,Article ID 751068,10pages,2013)。但是,至今还没有考察在空气污染条件下补充益生菌株的研究。
因此,市场上仍亟需可以有效地减少空气污染,特别是高水平的PM2.5污染物造成的肺部和/或全身性炎症的日用饮食补充剂。
发明内容
本发明涉及用于减少与PM2.5暴露相关的肺部和/或全身性炎症的组合物,所述组合物包含二十二碳六烯酸、益生菌株(如动物双歧杆菌乳双歧杆菌亚种)、维生素C和维生素E。优选地,根据本发明的组合物包含比例为50-500mg:5×107-5×1010CFU:10-250mg:1-100mg的二十二碳六烯酸、益生菌株、维生素C和维生素E。最优选地,根据本发明的组合物包含比例为75-150mg:1×109-1×1010CFU:30-150mg:4-20mg的二十二碳六烯酸、益生菌株、维生素C和维生素E。
本发明还涉及用于食品、药物、化妆品和饮料的补充剂,其包含根据本发明的组合物。
此外,一方面,本发明还提供了一种用于减少在有需要的受试者中与PM2.5污染物暴露相关的肺部和/或全身性炎症的方法,其包括给予受试者有效量的根据本发明的组合物。
另一方面,本发明进一步提供了根据本发明的组合物在制备用于减少在有需要的受试者中与PM2.5污染物暴露相关的肺部和/或全身性炎症的食品、药物、化妆品和饮料的补充剂中的用途。
本发明的其他特征和方面将在下文中进行更详细的讨论。
附图说明
图1:炎症相关的细胞因子/趋化因子的基因表达的聚类图;
图2:上调(深色条)和下调(浅色条)的基因表达的加权平均数。该平均数乘以考虑到与对照组相比显示显著的>3倍变化的基因数(1=无变化)的权重;
图3A:显示了DHA和BB12对基因表达的协同效应。将单一营养素产生的平均倍数变化(组2+3,白色区域)与组合营养素的倍数变化(组5,黑色区域)进行比较;
图3B:显示了BB12和Vit E/Vit C对基因表达的协同效应。将单一营养素产生的平均倍数变化(组3+4,白色区域)与组合营养素的倍数变化(组6,黑色区域)进行比较;
图3C:显示了DHA、BB12和Vit E/Vit C对基因表达的协同效应。将单一营养素产生的平均倍数变化(组2+3+4,白色区域)与组合营养素的倍数变化(组7,黑色区域)进行比较;
图4:代表8个组(组1-7和对照组)的肺切片。小黑点的存在表示被空气污染颗粒浸润。我们对组1切片中的PM2.5颗粒计数并指定为“+++”。其他切片(组2-7)根据相对于组1的PM2.5颗粒的存在进行评价;
图5:多个组的IL-10表达谱。根据制造商的建议,通过ELISA分析(eBioscience,目录号88-7105)测量血清IL-10水平。评估至少两份血清稀释液并绘制在使用已知的细胞因子浓度生成的标准曲线上。结果表示为不同组(横坐标)中的皮克/毫升(纵坐标),并代表两次独立测试的平均值。
具体实施方式
本发明涉及用于减少与PM2.5暴露相关的肺部和/或全身性炎症的组合物,包含二十二碳六烯酸、益生菌株(如动物双歧杆菌乳双歧杆菌亚种)、维生素C和维生素E。优选地,根据本发明的组合物包含比例为50-500mg:5×107-5×1010CFU:10-250mg:1-100mg的二十二碳六烯酸、益生菌株、维生素C和维生素E。最优选地,根据本发明的组合物包含比例为75-150mg:1×109-1×1010CFU:30-150mg:4-20mg的二十二碳六烯酸、益生菌株、维生素C和维生素E。
根据本发明的组合物可以呈多种适合作为食物和补充剂给予的形式,例如,组合物可以呈预制食品的形式,例如饼干、果汁、粉末饮料、糖果、冰激凌、干燥水果或蔬菜、功能性饮品、胶囊、片剂、囊片、棒、乳膏、凝胶、粉末、溶液、口胶等。因此,根据本发明的组合物还可以包括另外的组分。例如,所述另外的组分可以是选自益生菌、维生素、植物营养素、天然草药提取物,例如,番茄红素、姜黄、多酚等,或其组合的一种或多种另外的组分。
本发明还涉及用于食品、药物、化妆品和饮料的补充剂,其包含根据本发明的组合物。
根据本发明,二十二碳六烯酸(DHA)是Ω-3不饱和脂肪酸家族中的重要成员,其来源于植物或鱼/磷虾。Ω-3不饱和脂肪酸的抗炎和抗氧化作用已经被长期认可。
本发明可以采用多种益生菌株,例如乳杆菌(Lactobacillus)、双歧杆菌(Bifidobacterium)或酵母(Saccharomyces),优选为双歧杆菌,更优选为动物双歧杆菌乳双歧杆菌亚种。现在,益生菌株已经在全世界广泛用于婴儿制剂、膳食补充剂和发酵奶制品,其中动物双歧杆菌乳双歧杆菌亚种在技术上非常适合,其表现出发酵活性、高耐氧性、良好的稳定性和对酸和胆汁的高耐受性,其还被用作膳食补充剂中的冻干产品。而且,动物双歧杆菌乳双歧杆菌亚种对于食品的味道、外观或口感无不良影响,并且能够在益生菌食品中存活至该食品被食用。用于本发明的动物双歧杆菌乳双歧杆菌亚种可以粉末形式商购自例如Chr.Hansen。本发明已经证实益生菌株,优选为动物双歧杆菌乳双歧杆菌亚种增强了机体对普通呼吸道感染的抵抗力,以及减少了急性呼吸道感染的发病。
维生素C,也被称为抗坏血酸,例如可由商业渠道获得。
维生素E,也被称为生育酚,其具有四个亚组α、β、γ和δ,其中α-生育酚是生物活性和效力最强的,或α-生育酚,例如可由商业渠道获得。
出乎意料地,根据本发明的组合物中的上述四种营养组分的组合产生了协同作用,其减少了高水平的空气污染,特别是PM2.5污染物造成的肺部和/或全身性炎症。具体来说,根据本发明的组合物有助于减少空气污染相关的肺部炎症,其通过添加前后的两次互补测量、组织学分析和在炎症中起关键作用的基因,如Adipoq、CCL-7、IL-2、IL-4、IL-5、IL-10、IL-17(等)的肺mRNA曲线来评估。通过改变引起炎性过程本身的淋巴细胞群产生的细胞因子的水平,以及参与引起炎性过程本身的淋巴细胞群的极化,本发明的组合物还有助于减少与空气污染相关的全身性炎症。对该方面至关重要的是例如促炎TH1型细胞因子,如IL-12、TNF-α和IFN-γ,以及抗炎TH2型细胞因子IL-4和IL-10、TGF-β以及IgE免疫球蛋白的水平,其与炎症的变应类型相关。有趣的是,促炎TH1型细胞因子在短期内不特别地受不同的组合物配方的影响,而其他参数如产生变应的细胞因子IL-10的变化受到组合物的不同种类的显著影响。尽管无意于受到以下理论的限制,但是相信根据本发明的组合物的适合的种类不仅可以预防与PM2.5暴露相关的肺部和/或全身性炎症,而且还可以减少与PM2.5暴露相关的肺部和/或全身性炎症。
一方面,本发明还提供了一种用于减少在有需要的受试者中与PM2.5污染物暴露相关的肺部和/或全身性炎症的方法,其包括给予有效量的根据本发明的组合物。在优选实施方案中,DHA的有效剂量水平为50-500mg/天,优选为75-150mg/天;益生菌株(动物双歧杆菌乳双歧杆菌亚种)的有效剂量水平为5×107至5×1010CFU/天,优选为1×109至1×1010CFU/天;维生素C的有效剂量水平为10至250mg/天,优选为30至150mg/天;维生素E的有效剂量水平为1至100mg/天,优选为4至20mg/天。优选地,所述剂量为成人(70kg)的总剂量。
根据本发明的组合物可以递送至涉及所有年龄组的包括人受试者的哺乳动物。在本文中,术语“递送”一般是指机体对组合物的摄取。优选地,所述组合物经口服递送至受试者。患有对花粉或灰尘过敏、哮喘、过敏性鼻炎以及特应性皮炎等的人受试者特别适合每日使用所述组合物,其中受试者暴露于水平为25至500μg/m3,特别是100至500μg/m3的PM2.5污染物。生活在发展中国家的特定特大城市的人受试者暴露于高水平的PM2.5污染物,例如,北京的PM2.5的日平均水平为125μg/m3,测定的峰值甚至为500μg/m3。
本发明还提供了用于减少在有需要的受试者中与PM2.5污染物暴露相关的肺部和/或全身性炎症的方法,包括以下步骤:递送给受试者剂量水平为50-500mg/天,优选为75-150mg/天的DHA;剂量水平为5×107至5×1010CFU/天,优选为1×109至1×1010CFU/天的益生菌株(动物双歧杆菌乳双歧杆菌亚种);剂量水平为10至250mg/天,优选为30至150mg/天的维生素C;剂量水平为1至100mg/天,优选为4至20mg/天的维生素E。其中所述受试者暴露于水平为25至500μg/m3,特别是100至500μg/m3的PM2.5污染物。优选地,所述受试者是涉及所有年龄组的人受试者。
应理解的是,所述四种组分,即DHA、益生菌株、维生素C和维生素E可以同时、单独或以其任意组合给予所述受试者。在本发明的一个实施方案中,所述四种组分作为补充剂同时给予受试者,所述补充剂优选为胶囊、片剂、囊片、棒、口胶、乳膏、凝胶、粉末或溶液等形式。在本发明的优选的实施方案中,DHA和动物双歧杆菌乳双歧杆菌亚种在混合并且然后包封成胶囊、片剂、粉末或凝胶形式后一起递送,而维生素C和维生素E在混合成口胶、咀嚼物或食物形式后一起递送。根据本发明,也可以将DHA、维生素C和维生素E干混并随后组装成口胶、咀嚼物或食物形式后一起递送,而动物双歧杆菌乳双歧杆菌亚种分开递送。上述过程,例如干混或包封过程都是本领域技术人员熟知的常规方法。
在另一个方面,本发明还提供了根据本发明的组合物在制备用于减少在有需要的受试者中与PM2.5污染物暴露相关的肺部和/或全身性炎症的食品、药物、化妆品和饮料的补充剂中的用途。
实施例
本发明的组合物的制备
原料:DHA;动物双歧杆菌乳双歧杆菌亚种;维生素C;和维生素E。
实施例1:通过本领域技术人员熟知的常规方法,将DHA和动物双歧杆菌乳双歧杆菌亚种混合并包封成胶囊、片剂、粉末、凝胶形式,而维生素C和维生素E混合成口胶、咀嚼物或食物形式。
实施例2:通过本领域技术人员熟知的常规方法,将DHA、维生素C和维生素E干混并组装成口胶、咀嚼物或其他食物形式,而动物双歧杆菌乳双歧杆菌亚种以胶囊、片剂或食物形式递送。
实施例3:通过本领域技术人员熟知的常规方法,将动物双歧杆菌乳双歧杆菌亚种、维生素C和维生素E干混并组装成粉末、口胶、咀嚼物或其他食物形式,而DHA以胶囊、油、片剂或食物形式递送。
实施例4-5的制备方法与实施例1-2相同,只是四种营养素的量不同,如表1中所列举。
表1:实施例中四种营养素的量
基于动物模型对由PM2.5暴露引起的体内影响的研究
第一步,我们采用熟知的用于污染研究的体内动物模型,其涉及通过咽部吸入等渗生理盐水气溶胶(假实验小鼠组)或包含PM2.5的气溶胶(PM2.5处理的小鼠组)处理雌性BALB/c小鼠(7-8周龄)。模拟污染的郊区区域的大气微粒物质的细小颗粒物质PM2.5(中值粒径2.8μm)购自国家标准和技术研究所(National Institute of Standards andTechnologies,SRM 2786,NIST,Gaithersburg,Md,USA)。细小颗粒的收集、组成和储存描述于分析证书中(https://www-s.nist.gov/srmors/view_cert.cfm?srm=2786)。
小鼠被随机分成8个不同的处理组(每组5只小鼠,参见表2),确保每组的平均体重很好地匹配。在咽部吸入前,7-8周龄小鼠以不同设计的饮食处理30天,如表2所示,所述饮食组成基于普通的小鼠饮食,通常以颗粒形式提供,其中加入本发明的成分,所述咽部吸入在第0、3和6天进行,共吸入三次100mg PM2.5的50ml等渗生理盐溶液或50ml等渗生理盐溶液(假实验组)。下文是对咽部吸入过程的描述。
在处理期间,用异氟烷麻醉动物并借助机械固定器保持为垂直姿势。用镊子轻轻夹住舌头并拉出,并以这样的方式固定在嘴的一侧,即使舌头本身的根部可见。在舌头根部上递送处理溶液,并且经过至少两个完整的呼吸周期的时间,以确保溶液被吸入而不是被吞咽。在苏醒后,恢复给予动物指定的饮食。
我们选择咽部吸入以模拟空气污染在肺中的作用以尝试实施最小的侵入性过程,但证明了与其他技术如气管内接种(其中将进行更重度的麻醉接着是气管内插管)一样有效。
该方法使我们能评价设计的饮食是否保护肺部和肝脏免受污染。在处死后,即末次吸入后3天,收集肺和血清样品并迅速冷冻。解冻后,处理样品用于生化、免疫化学分析,以及用于评估炎性细胞因子的水平。对于组织学,通过低温恒温器切割连续的肺切片,固定在载玻片上并使用Carazzi苏木精和伊红染色。
表2:不同小鼠组的饮食和空气污染水平
组编号 | 饮食 | 空气污染水平 |
对照组 | 基础 | 假实验 |
组1 | 基础 | PM2.5,100μg/m3 |
组2 | 基础+DHA | PM2.5,100μg/m3 |
组3 | 基础+BB12 | PM2.5,100μg/m3 |
组4 | 基础+Vit E/Vit C | PM2.5,100μg/m3 |
组5 | 基础+DHA+BB12 | PM2.5,100μg/m3 |
组6 | 基础+BB12+Vit E/VitC | PM2.5,100μg/m3 |
组7 | 基础+DHA+BB12+Vit E/Vit C | PM2.5,100μg/m3 |
评价方案
该方案使我们能够评价设计的饮食是否能够针对PM2.5污染物保护肺和肝脏。
处死后,如上所述收集的血清和肺样品用于生化、组织学和免疫化学分析,评价炎症细胞因子的水平。通过H&E染色分析属于不同的处理组和对照小鼠的小鼠肺活组织切片,以精确地评价形态和炎症变化。而且,对血清样品进行生化分析。
本实验检测的炎症生物标记物如下所述:
大量小鼠细胞因子和趋化因子的肺基因表达(Qiagen plates,SABiosciences),共84种标记物,其中以下与炎症途径非常相关:
细胞因子:Adipoq、Bmp7、Il10、Il11、Il17a、Il2、Il22、Il23a、Il24、Il4、Il5、Lif、Tnfrsf11b、Tnfsf10;
趋化因子:Ccl1、Ccl12、Ccl17、Ccl2、Ccl20、Ccl7、Cxcl1、Cxcl10、Cxcl5、Cxcl9;
血清细胞因子/趋化因子(咽部吸入暴露之前和之后):TGF-b、IFNγ、TNF-α、IL-10、IL-5、IL-4、IL-6、IL-1β。
测试结果
本发明的组合物中的这四种类型的营养素的组合产生了协同作用,减少了高水平空气污染导致的肺部炎症,并且还可以对TH2全身过敏反应具有有益作用。认为根据本发明的组合物不仅能够预防肺部和/或全身性炎症,而且还能减少与PM2.5相关的肺部和/或全身性炎症。
在肺中的基因表达
我们首先使用SABioscience标准板PAMM150Z(细胞因子和趋化因子)评估了在炎症中起到关键作用的基因的肺mRNA谱。基于倍数变化表达值在组1(PM2.5,对照饮食)相对于对照组(洁净空气,对照饮食)中高于3,在84种标记物中选择23个基因的亚组。
图1显示了这些基因在所有组中的表达的聚类示意图。被文献证据分类为促炎或抗炎的细胞因子/趋化因子分别突出显示为浅灰色或深灰色。被报导发挥促炎和抗炎效应二者的那些被突出显示为白色。
如根据选择标准所预期的,对照组和组1在基因表达方面几乎具有镜像模式。有趣的是,组4以及尤其是组7的列与对照组之间的比较表明特定饮食的递送如何看起来更有效地通过使炎性细胞因子/趋化因子的表达水平回到对照水平而对抗PM2.5暴露。多个组表达模式的相似性的更清晰的可视化由3色版的聚类图(浅灰-黑-深灰)提供,插入该图来说明图1。
在被分析的基因中,暴露于PM2.5使Ccl7、AdipoQ和Il23a的表达急剧升高,其水平在不同饮食后部分或全部恢复。在文献中已描述所有这些基因在促进气道的炎性疾病中的作用,与我们的研究结果一致。
CCL7,Ccl7基因的产物,是通常已知在炎症期间吸引单核细胞/巨噬细胞的趋化因子。文献报导暴露于过敏原和臭氧诱导的氧化应激提高气道上皮细胞的CCL7产生(Michalec等人,CCL7and CXCL10orchestrate oxidative stress-induced neutrophiliclung inflammation.J Immunol.2002;168(2):846-852;Stafford等人,Monocytechemotactic protein-3(MCP-3)/fibroblast-induced cytokine(FIC)in eosinophilicinflammation of the airways and the inhibitory effects of an anti-MCP-3/FICantibody.J Immunol.1997;158(10):4953-4960),并且这导致嗜酸性粒细胞和嗜中性粒细胞在肺中的募集,其促进炎症(Michalec等人,CCL7and CXCL10orchestrate oxidativestress-induced neutrophilic lung inflammation.J Immunol.2002;168(2):846-852;Mercer等人,Proteinase-activated receptor-1,CCL2,and CCL7regulate acuteneutrophilic lung inflammation.Am J Respir Cell Mol Biol.2014;50(1):144-157)。
对于Adipoq,该基因编码脂联素,一种由脂肪组织产生的激素样蛋白,其在炎症中的作用是有争议的。事实上,虽然主要具有抗炎功能,但冲突证据报导了脂联素在特定条件下的促炎作用(Ehling等人,The potential of adiponectin in drivingarthritis.J.Immunol.2006;176(7):4468-4478;Garcia and Sood,Adiponectin inpulmonary disease and critically ill patients.Curr Med Chem.2012;19(32):5493-5500;Sood等人,Serum adiponectin is Associated with Adverse Outcomes of Asthmain Men but Not in Women.Front Pharmacol.2011;2:55)。有趣的是,已经显示不仅脂肪细胞表达脂联素,而且气道上皮细胞也表达脂联素,其在慢性阻塞性肺病(COPD)—一种肺部的慢性炎性疾病中升高(Miller等人,Adiponectin and functional adiponectinreceptor 1are expressed by airway epithelial cells in chronic obstructivepulmonary disease.J Immunol.2009;182(1):684-691)。
Il23a编码异源二聚体细胞因子IL23的α(或p19)亚单位,其在许多慢性炎症疾病,包括哮喘中具有致病作用(Nakajima和Hirose.Role of IL-23and Th17Cells in AirwayInflammation in Asthma.Immune Netw.2010;10(1):1-4)。发现Il23a mRNA在暴露于过敏刺激的小鼠的肺中上调,在肺中其引发嗜中性粒细胞和嗜曙红细胞介导的炎症反应(Nakajima和Hirose.Role of IL-23and Th17Cells in Airway Inflammation inAsthma.Immune Netw.2010;10(1):1-4;Peng等人,IL-23signaling enhancesTh2polarization and regulates allergic airway inflammation.Cell Res.2010;20(1):62-71;IL-23and Th17cells enhance Th2-cell-mediated eosinophilic airwayinflammation in mice.Am J Respir Crit Care Med.2008;178(10):1023-1032)。
一致地,IL23缺乏或中和导致气道炎症降低(Peng等人,IL-23signalingenhances Th2polarization and regulates allergic airway inflammation.CellRes.2010;20(1):62-71;IL-23and Th17cells enhance Th2-cell-mediatedeosinophilic airway inflammation in mice.Am J Respir Crit Care Med.2008;178(10):1023-1032)。
值得注意的是,在基因Ccl12响应PM2.5和测试的营养素的表达中观察到有趣的趋势。事实上,虽然在组1中没有急剧升高(截止点小于3),但其在使用不同饮食处理的所有其他组中变得强烈下调(尤其在接受BB12的组3中)。
鼠科Ccl12基因编码与人CCL2共享高度同源性的趋化因子(Sarafi等人,Murinemonocyte chemoattractant protein(MCP)-5:a novel CC chemokine that is astructural and functional homologue of human MCP-1.J Exp Med.1997;185(1):99-109),其表达在肺的炎性病症中升高(Rose等人,Significant involvement of CCL2(MCP-1)in inflammatory disorders of the lung.Microcirculation.2003;10(3-4):273-288)。此外,在特发性肺纤维化的小鼠模型中,发现CCL12本身募集纤维细胞并介导纤维化反应(Moore等人,The role of CCL12in the recruitment of fibrocytes and lungfibrosis.Am J Respir Cell Mol Biol.2006;35(2):175-181)。长期暴露于空气污染物会使气道暴露于慢性炎症,并随后纤维化,阻碍正常的肺部功能。因此,持续服用可以拮抗促纤维化剂的营养素可以代表预防或管理这样的疾病的有前途的策略。
图2通过显示每组与对照条件的整体接近性,总结了聚类图数据。两个相似度系数分别通过对每组中上调和下调的基因表达取平均值来计算。
四种营养素的不同组合显示对基因表达的整体协同效应,分别如图3A(组2和组3相对于组5)、3B(组3和组4相对于组6)和3C(组2、组3和组4相对于组7)所示。
肺组织学分析
冲洗来自假实验组(对照组)和PM2.5处理的小鼠(组1至7)的肺,并适当地收集和储存在液氮中。通过低温恒温器将每个假实验组和PM2.5暴露的肺样品切割为10μm的连续切片,固定在载玻片上并使用Carazzi苏木精和伊红染色。Nikon Eclipse E600显微镜用于分析。在40X放大倍率下拍摄照片。
观察到随机(或零星的)微粒物质吞没在肺泡巨噬细胞中,尤其是在组1(PM2.5处理组)中,证据也可以在其他各组的切片中见到(图4b、d和f)。一些明显的形态变化存在于炎性细胞的偶尔的浸润中。
血清炎性细胞因子
代表所谓的促炎TH-1细胞因子,如IFN-g、TNF-α和IL-1,以及与IgE-介导的过敏反应相关的TH-2细胞因子,如IL-4、IL-5和IL-10的一系列细胞因子,与免疫抑制细胞因子TGF-β一起已经过初步测试并在已经历特定饮食方案的PM2.5注射的动物中测量。作为一个实例,我们显示了IL-10的血清浓度,IL-10是过敏性炎症的基本标记物(图5)。从浓度水平可以推断出使用特定的饮食预处理(组3、组4和尤其是组7中的四种成分的组合)可以潜在地预防过敏性炎症反应的发作。虽然我们未观察到严格地由PM2.5粉末引起的血清细胞因子的有意义的变化,但应强调的是,在该研究中分析的正常Balb/c小鼠已经表达的IL-10的平均水平显著高于平常的(2-3倍,参照例如Schloot等人,Diabetes Metab Res Rev 2002;18:64–70.),使得在经历特定饮食方案的某些组的小鼠中的IL-10的下降甚至更重要。此外,还应考虑到的是,PM2.5给予的时限相对短以产生和/或觉察到可测量的量的另外的细胞因子,特别是模拟慢性过敏反应的TH2细胞因子,如IL-4和IL-5。
应认识到前述实施例的细节是出于说明的目的而给出的,无意于作为本发明的范围的限制。尽管上文仅详细描述了本发明的几个示例性实施方案,但是本领域技术人员将容易地认识到在不实质上背离本发明的新颖的教导和优势的情况下,实施例可以进行许多改进。例如,就一个实施例描述的特征可以结合到本发明的任何其他实施例中。
相应地,所有的这些改进意在包括在本发明的范围内,该范围由以下权利要求及其等同的技术方案所限定。而且,应认识到,可以想到许多不能实现某些技术方案,特别是理想的实施方案的所有优点的实施方案,缺少具体的优点并不能理解成必然意味着这样的实施方案落在本发明的范围之外。在不背离本发明的范围的情况下,上述技术方案可以进行各种变化,这意味着包含在上述说明中的所有内容应解释为说明性的并没有限制的意思。
参考文献
1.Rutkowski等人,Allergic diseases:the price of civilisationalprogress,Postep Derm Allergol 2014;XXXI,2:77–83.
2.WHO,2005,参见:http://www.who.int/phe/health_topics/outdoorair/outdoorair_aqg/en/
3.Possamai等人,Antioxidant intervention compensates oxidative stressin blood of subjects exposed to emissions from a coal electric-power plant inSouth Brazil,Environ Toxicol Pharmacol.2010Sep;30(2):175-80.
4.Sienra-Monge等人,Antioxidant supplementation and nasal inflammatoryresponses among young asthmatics exposed to high levels of ozone,Clin.Exp.Immunol.2004Nov;138(2):317-22.
5.Zhang W.等人.Nutrition Solutions to Counter Health Impact of AirPollution:Scientific Evidence of Marine Omega-3Fatty Acids and VitaminsMinimizing Some Harms of PM2.5,J.Food Nutr Sci,2015,2(2):1-6.
6.Jungersen等人,The Science behind the Probiotic StrainBifidobacterium animalis subsp.lactis BB-Microorganisms,2014,2,92-110.
7.Mortaz等人,Probiotics in the Management of Lung Diseases,Mediatorsof Inflammation,vol.2013,Article ID 751068,10pages,2013.
8.Michalec L,Choudhury BK,Postlethwait E,Wild JS,Alam R,Lett-Brown M和Sur S.CCL7and CXCL10orchestrate oxidative stress-induced neutrophilic lunginflammation.J Immunol.2002;168(2):846-852.
9.Stafford S,Li H,Forsythe PA,Ryan M,Bravo R和Alam R.Monocytechemotactic protein-3(MCP-3)/fibroblast-induced cytokine(FIC)in eosinophilicinflammation of the airways and the inhibitory effects of an anti-MCP-3/FICantibody.J Immunol.1997;158(10):4953-4960.
10.Mercer PF,Williams AE,Scotton CJ,Jose RJ,Sulikowski M,Moffatt JD,Murray LA和Chambers RC.Proteinase-activated receptor-1,CCL2,and CCL7regulateacute neutrophilic lung inflammation.Am J Respir Cell Mol Biol.2014;50(1):144-157.
11.Ehling A,Schaffler A,Herfarth H,Tarner IH,Anders S,Distler O,PaulG,Distler J,Gay S,Scholmerich J,Neumann E和Muller-Ladner U.The potential ofadiponectin in driving arthritis.J Immunol.2006;176(7):4468-4478.
12.Garcia P和Sood A.Adiponectin in pulmonary disease and criticallyill patients.Curr Med Chem.2012;19(32):5493-5500.
13.Sood A,Dominic E,Qualls C,Steffes MW,Thyagarajan B,Smith LJ,LewisCE和Jacobs DR,Jr.Serum Adiponectin is Associated with Adverse Outcomes ofAsthma in Men but Not in Women.Front Pharmacol.2011;2:55.
14.Miller M,Cho JY,Pham A,Ramsdell J和Broide DH.Adiponectin andfunctional adiponectin receptor 1are expressed by airway epithelial cells inchronic obstructive pulmonary disease.J Immunol.2009;182(1):684-691.
15.Nakajima H和Hirose K.Role of IL-23and Th17Cells in AirwayInflammation in Asthma.Immune Netw.2010;10(1):1-4.
16.Peng J,Yang XO,Chang SH,Yang J和Dong C.IL-23signaling enhancesTh2polarization and regulates allergic airway inflammation.Cell Res.2010;20(1):62-71.
17.Wakashin H,Hirose K,Maezawa Y,Kagami S,Suto A,Watanabe N,Saito Y,Hatano M,Tokuhisa T,Iwakura Y,Puccetti P,Iwamoto I和Nakajima H.IL-23andTh17cells enhance Th2-cell-mediated eosinophilic airway inflammation inmice.Am J Respir Crit Care Med.2008;178(10):1023-1032.
18.Sarafi MN,Garcia-Zepeda EA,MacLean JA,Charo IF和Luster AD.Murinemonocyte chemoattractant protein(MCP)-5:a novel CC chemokine that is astructural and functional homologue of human MCP-1.J Exp Med.1997;185(1):99-109.
19.Rose CE,Jr.,Sung SS和Fu SM.Significant involvement of CCL2(MCP-1)in inflammatory disorders of the lung.Microcirculation.2003;10(3-4):273-288.
20.Moore BB,Murray L,Das A,Wilke CA,Herrygers AB和Toews GB.The roleof CCL12in the recruitment of fibrocytes and lung fibrosis.Am J Respir CellMol Biol.2006;35(2):175-181.
Claims (7)
1.一种用于减少与PM2.5暴露相关的肺部和/或全身性炎症的组合物,其包含二十二碳六烯酸、益生菌株、维生素C和维生素E,其中所述益生菌株优选为动物双歧杆菌乳双歧杆菌亚种。
2.根据权利要求1所述的组合物,其中,所述组合物包含比例为50-500mg:5×107-5×1010CFU:10-250mg:1-100mg的二十二碳六烯酸、益生菌株、维生素C和维生素E,优选比例为75-150mg:1×109-1×1010CFU:30-150mg:4-20mg的二十二碳六烯酸、益生菌株、维生素C和维生素E。
3.根据权利要求1或2所述的组合物,其中,所述组合物适用于作为食品和补充剂给予,例如,所述组合物呈饼干、果汁、粉末饮料、糖果、冰激凌、干燥水果和蔬菜、功能性饮品、胶囊、片剂、囊片、棒、乳膏、凝胶、粉末、溶液或口胶的形式,并且所述组合物优选地包括另外的组分,所述另外的组分选自益生菌、维生素、植物营养素、天然草药提取物,例如,番茄红素、姜黄或多酚,或其组合。
4.一种用于预防和减少在有需要的受试者中与PM2.5污染物暴露相关的全身性炎症关联的肺和/或过敏症状的方法,其包括给予有效量的根据权利要求1或2所述的组合物。
5.根据权利要求4所述的方法,其中所述受试者暴露于水平为25至500μg/m3,特别是100至500μg/m3的PM2.5污染物。
6.根据权利要求4或5所述的方法,其中所述受试者是人受试者,其生活在具有日平均水平为125μg/m3,测定的峰值甚至为500μg/m3的PM2.5污染物的环境中。
7.根据权利要求1至3中任一项所述的组合物在制备用于预防和减少在有需要的受试者中与PM2.5污染物暴露相关的全身性炎症关联的肺和/或过敏症状的食品、药物、化妆品和饮料的补充剂中的用途。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201510511609 | 2015-08-19 | ||
CN201510511609X | 2015-08-19 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN106256352A true CN106256352A (zh) | 2016-12-28 |
Family
ID=57713909
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201610695981.5A Pending CN106256352A (zh) | 2015-08-19 | 2016-08-19 | 用于减少与pm2.5暴露相关的肺部和/或全身性炎症的组合物及其用途 |
Country Status (2)
Country | Link |
---|---|
CN (1) | CN106256352A (zh) |
WO (1) | WO2017028813A1 (zh) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113521113A (zh) * | 2020-04-15 | 2021-10-22 | 丰华生物科技股份有限公司 | 使用乳酸菌菌株的液态培养物来抗发炎以及治疗发炎性障碍 |
CN114046596A (zh) * | 2021-11-17 | 2022-02-15 | 重庆大学 | 基于trp生化指标检测的室内空气质量控制系统及方法 |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2023237673A1 (en) * | 2022-06-10 | 2023-12-14 | Dsm Ip Assets B.V. | Combinations comprising vitamin c and bifidobacterium animalis ssp. lactis |
WO2023237681A1 (en) * | 2022-06-10 | 2023-12-14 | Dsm Ip Assets B.V. | Combinations comprising vitamin c and bifidobacterium animalis ssp. lactis |
WO2023237677A1 (en) * | 2022-06-10 | 2023-12-14 | Dsm Ip Assets B.V. | Combinations comprising vitamin c and bifidobacterium animalis ssp. lactis |
WO2023237680A1 (en) * | 2022-06-10 | 2023-12-14 | Dsm Ip Assets B.V. | Combinations comprising vitamin c and bifidobacterium animalis ssp. lactis |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104168905A (zh) * | 2011-06-10 | 2014-11-26 | 杜邦营养生物科学有限公司 | 使用乳双歧杆菌bl-04治疗呼吸道疾病 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2707721A1 (en) * | 2010-07-14 | 2010-09-21 | Nutritech Solutions Ltd. | Fermented milk beverage |
CN102090558A (zh) * | 2010-12-09 | 2011-06-15 | 上海交大昂立股份有限公司 | 一种含益生菌、dha和乳铁蛋白的组合物及其应用 |
CN102144670A (zh) * | 2011-02-28 | 2011-08-10 | 澳优乳业(中国)有限公司 | 一种益生菌配方奶粉及其制造方法 |
CN104206539A (zh) * | 2014-08-14 | 2014-12-17 | 澳优乳业(中国)有限公司 | 一种益生菌婴幼儿奶粉 |
CN104824157A (zh) * | 2015-06-02 | 2015-08-12 | 内蒙古蒙牛乳业(集团)股份有限公司 | 儿童常温酸奶及其制备方法 |
-
2016
- 2016-08-19 CN CN201610695981.5A patent/CN106256352A/zh active Pending
- 2016-08-19 WO PCT/CN2016/096025 patent/WO2017028813A1/en active Application Filing
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104168905A (zh) * | 2011-06-10 | 2014-11-26 | 杜邦营养生物科学有限公司 | 使用乳双歧杆菌bl-04治疗呼吸道疾病 |
Non-Patent Citations (2)
Title |
---|
ESMAEIL MORTAZ等: "Probiotics in the Management of Lung Diseases", 《MEDIATORS OF INFLAMMATION》 * |
ZHANG WEIGUO等: "Nutrition Solutions to Counter Health Impact of Air Pollution: Scientific Evidence of Marine Omega-3 Fatty Acids and Vitamins Alleviating Some Harmful Effects of PM2.5", 《INTERNATIONAL JOURNAL OF FOOD AND NUTRITIONAL SCIENCE》 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113521113A (zh) * | 2020-04-15 | 2021-10-22 | 丰华生物科技股份有限公司 | 使用乳酸菌菌株的液态培养物来抗发炎以及治疗发炎性障碍 |
CN114046596A (zh) * | 2021-11-17 | 2022-02-15 | 重庆大学 | 基于trp生化指标检测的室内空气质量控制系统及方法 |
Also Published As
Publication number | Publication date |
---|---|
WO2017028813A1 (en) | 2017-02-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106256352A (zh) | 用于减少与pm2.5暴露相关的肺部和/或全身性炎症的组合物及其用途 | |
Bustamante et al. | Probiotics and prebiotics potential for the care of skin, female urogenital tract, and respiratory tract | |
US11197901B2 (en) | Active substance of Lactobacillus paracasei GKS6, a composition comprising thereof and its use for promoting longevity | |
Gleeson et al. | Daily probiotic’s (Lactobacillus casei Shirota) reduction of infection incidence in athletes | |
Gleeson et al. | Effects of a Lactobacillus salivarius probiotic intervention on infection, cold symptom duration and severity, and mucosal immunity in endurance athletes | |
ES2423497T3 (es) | Uso de Lactobacillus para aumentar la absorción de un metal elegido entre Fe, Zn, Ca y sus iones | |
CN104168905B (zh) | 使用乳双歧杆菌bl-04治疗呼吸道疾病 | |
US20210138002A1 (en) | Preparation for the treatment of inflammatory bowel disease using a whole plant fibre extract from sugarcane | |
Leite et al. | Probiotics and sports: A new magic bullet? | |
ES2873889T3 (es) | Uso de probióticos en el tratamiento y/o la prevención de la enfermedad de la psoriasis | |
Möller et al. | Supplementation of probiotics and its effects on physically active individuals and athletes: systematic review | |
US20220143114A1 (en) | Active substance of lactobacillus plantarum gkm3, a composition comprising thereof and its use for promoting longevity | |
Gill et al. | High-dose probiotic supplementation containing Lactobacillus casei for 7 days does not enhance salivary antimicrobial protein responses to exertional heat stress compared with placebo | |
ES2893866T3 (es) | Composición de lactobacillus que permite favorecer el crecimiento juvenil humano y animal en caso de malnutrición | |
CN109310714A (zh) | 用于治疗和预防胃肠炎症的普氏粪杆菌菌株cncm i-4573 | |
Shimizu et al. | The effects of Lactobacillus pentosus strain b240 and appropriate physical training on salivary secretory IgA levels in elderly adults with low physical fitness: a randomized, double-blind, placebo-controlled trial | |
Moreira et al. | Allergy in marathon runners and effect of Lactobacillus GG supplementation on allergic inflammatory markers | |
CN107206034A (zh) | 包含双歧杆菌的免疫调节组合物 | |
CN107319118A (zh) | 一种宠物狗专用食粮及其制备方法 | |
Nova et al. | Effects of a nutritional intervention with yogurt on lymphocyte subsets and cytokine production capacity in anorexia nervosa patients | |
ES2549541T3 (es) | Cepa de Lactobacillus fermentum CECT 7472 con propiedades probióticas | |
Smarkusz et al. | Probiotic strains as the element of nutritional profile in physical activity–new trend or better sports results? | |
JP2018012681A (ja) | 経口組成物 | |
RU2322995C1 (ru) | Биопрепарат ветеринарного назначения и способ профилактики желудочно-кишечных болезней новорожденных телят с его применением | |
US20210299192A1 (en) | Composition for anti-oxidation, oral health, immunity regulation and exercise promotion, and uses thereof |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20161228 |
|
RJ01 | Rejection of invention patent application after publication |