CN101693103A - Improvement of completeness of intestinal barrier - Google Patents
Improvement of completeness of intestinal barrier Download PDFInfo
- Publication number
- CN101693103A CN101693103A CN200910209324A CN200910209324A CN101693103A CN 101693103 A CN101693103 A CN 101693103A CN 200910209324 A CN200910209324 A CN 200910209324A CN 200910209324 A CN200910209324 A CN 200910209324A CN 101693103 A CN101693103 A CN 101693103A
- Authority
- CN
- China
- Prior art keywords
- compositions
- oligosaccharide
- protein
- acid
- described compositions
- 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.)
- Granted
Links
- 210000005027 intestinal barrier Anatomy 0.000 title abstract description 8
- 230000007358 intestinal barrier function Effects 0.000 title abstract description 8
- 230000006872 improvement Effects 0.000 title abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 104
- 229920001542 oligosaccharide Polymers 0.000 claims abstract description 75
- 150000002482 oligosaccharides Chemical class 0.000 claims abstract description 75
- 238000000034 method Methods 0.000 claims abstract description 36
- 235000018102 proteins Nutrition 0.000 claims description 20
- 102000004169 proteins and genes Human genes 0.000 claims description 20
- 108090000623 proteins and genes Proteins 0.000 claims description 20
- 230000002378 acidificating effect Effects 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 15
- 150000001720 carbohydrates Chemical class 0.000 claims description 15
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 claims description 15
- 150000002632 lipids Chemical class 0.000 claims description 14
- 150000002772 monosaccharides Chemical group 0.000 claims description 14
- 229920001202 Inulin Polymers 0.000 claims description 13
- 235000014633 carbohydrates Nutrition 0.000 claims description 13
- 229940029339 inulin Drugs 0.000 claims description 13
- 235000000346 sugar Nutrition 0.000 claims description 13
- 238000011282 treatment Methods 0.000 claims description 10
- 229930182830 galactose Natural products 0.000 claims description 9
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 235000013350 formula milk Nutrition 0.000 claims description 8
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 238000006116 polymerization reaction Methods 0.000 claims description 6
- 239000000413 hydrolysate Substances 0.000 claims description 5
- 235000001014 amino acid Nutrition 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 238000002360 preparation method Methods 0.000 claims description 4
- 108010082495 Dietary Plant Proteins Proteins 0.000 claims description 3
- 102000004407 Lactalbumin Human genes 0.000 claims description 3
- 108090000942 Lactalbumin Proteins 0.000 claims description 3
- 239000002777 nucleoside Substances 0.000 claims description 3
- 150000003833 nucleoside derivatives Chemical class 0.000 claims description 3
- 239000002773 nucleotide Substances 0.000 claims description 3
- 125000003729 nucleotide group Chemical group 0.000 claims description 3
- 229920000642 polymer Polymers 0.000 claims description 3
- 108010079058 casein hydrolysate Proteins 0.000 claims description 2
- AIHDCSAXVMAMJH-GFBKWZILSA-N levan Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@@H]1[C@@H](O)[C@H](O)[C@](CO)(CO[C@@H]2[C@H]([C@H](O)[C@@](O)(CO)O2)O)O1 AIHDCSAXVMAMJH-GFBKWZILSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims 2
- 230000007062 hydrolysis Effects 0.000 claims 2
- 238000006460 hydrolysis reaction Methods 0.000 claims 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 abstract description 81
- 235000021342 arachidonic acid Nutrition 0.000 abstract description 40
- 229940114079 arachidonic acid Drugs 0.000 abstract description 40
- 230000004888 barrier function Effects 0.000 abstract description 39
- JAZBEHYOTPTENJ-JLNKQSITSA-N all-cis-5,8,11,14,17-icosapentaenoic acid Chemical compound CC\C=C/C\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O JAZBEHYOTPTENJ-JLNKQSITSA-N 0.000 abstract description 33
- 235000020673 eicosapentaenoic acid Nutrition 0.000 abstract description 33
- 229960005135 eicosapentaenoic acid Drugs 0.000 abstract description 33
- JAZBEHYOTPTENJ-UHFFFAOYSA-N eicosapentaenoic acid Natural products CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O JAZBEHYOTPTENJ-UHFFFAOYSA-N 0.000 abstract description 33
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 abstract 1
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 abstract 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 abstract 1
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 abstract 1
- 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 description 32
- 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 description 32
- 235000020978 long-chain polyunsaturated fatty acids Nutrition 0.000 description 20
- 102000004388 Interleukin-4 Human genes 0.000 description 18
- 108090000978 Interleukin-4 Proteins 0.000 description 18
- 229940028885 interleukin-4 Drugs 0.000 description 18
- 230000000968 intestinal effect Effects 0.000 description 17
- 210000003097 mucus Anatomy 0.000 description 14
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 13
- 150000004666 short chain fatty acids Chemical class 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 12
- 235000014113 dietary fatty acids Nutrition 0.000 description 11
- 229930195729 fatty acid Natural products 0.000 description 11
- 239000000194 fatty acid Substances 0.000 description 11
- 150000004665 fatty acids Chemical class 0.000 description 11
- 230000035699 permeability Effects 0.000 description 11
- 108010063954 Mucins Proteins 0.000 description 10
- 235000019197 fats Nutrition 0.000 description 10
- 235000013305 food Nutrition 0.000 description 10
- 239000005715 Fructose Substances 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 210000001072 colon Anatomy 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 210000000981 epithelium Anatomy 0.000 description 9
- 230000004907 flux Effects 0.000 description 9
- 229960003082 galactose Drugs 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 229930091371 Fructose Natural products 0.000 description 8
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 8
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 8
- 150000002402 hexoses Chemical class 0.000 description 8
- 229920001503 Glucan Polymers 0.000 description 7
- 108010008705 Mucin-2 Proteins 0.000 description 7
- 102100034263 Mucin-2 Human genes 0.000 description 7
- 230000006378 damage Effects 0.000 description 7
- 210000003608 fece Anatomy 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- 235000001727 glucose Nutrition 0.000 description 7
- 206010002198 Anaphylactic reaction Diseases 0.000 description 6
- 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 6
- 230000036783 anaphylactic response Effects 0.000 description 6
- 208000003455 anaphylaxis Diseases 0.000 description 6
- 210000001842 enterocyte Anatomy 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 210000004877 mucosa Anatomy 0.000 description 6
- 235000016709 nutrition Nutrition 0.000 description 6
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 5
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 5
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 230000032050 esterification Effects 0.000 description 5
- 238000005886 esterification reaction Methods 0.000 description 5
- 230000002349 favourable effect Effects 0.000 description 5
- 235000020256 human milk Nutrition 0.000 description 5
- 210000004251 human milk Anatomy 0.000 description 5
- 229910052739 hydrogen Inorganic materials 0.000 description 5
- 239000001257 hydrogen Substances 0.000 description 5
- 210000003405 ileum Anatomy 0.000 description 5
- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 description 5
- 230000035764 nutrition Effects 0.000 description 5
- 229920001277 pectin Polymers 0.000 description 5
- 235000010987 pectin Nutrition 0.000 description 5
- 239000001814 pectin Substances 0.000 description 5
- 230000004936 stimulating effect Effects 0.000 description 5
- 208000030507 AIDS Diseases 0.000 description 4
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 4
- SRBFZHDQGSBBOR-IOVATXLUSA-N D-xylopyranose Chemical compound O[C@@H]1COC(O)[C@H](O)[C@H]1O SRBFZHDQGSBBOR-IOVATXLUSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 230000002052 anaphylactic effect Effects 0.000 description 4
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 4
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 230000002079 cooperative effect Effects 0.000 description 4
- 235000005911 diet Nutrition 0.000 description 4
- 238000000855 fermentation Methods 0.000 description 4
- 230000004151 fermentation Effects 0.000 description 4
- 238000012856 packing Methods 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 230000000638 stimulation Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 3
- AEMOLEFTQBMNLQ-YMDCURPLSA-N D-galactopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-YMDCURPLSA-N 0.000 description 3
- PNNNRSAQSRJVSB-SLPGGIOYSA-N Fucose Natural products C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C=O PNNNRSAQSRJVSB-SLPGGIOYSA-N 0.000 description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- SHZGCJCMOBCMKK-DHVFOXMCSA-N L-fucopyranose Chemical compound C[C@@H]1OC(O)[C@@H](O)[C@H](O)[C@@H]1O SHZGCJCMOBCMKK-DHVFOXMCSA-N 0.000 description 3
- SQVRNKJHWKZAKO-PFQGKNLYSA-N N-acetyl-beta-neuraminic acid Chemical compound CC(=O)N[C@@H]1[C@@H](O)C[C@@](O)(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO SQVRNKJHWKZAKO-PFQGKNLYSA-N 0.000 description 3
- SUHQNCLNRUAGOO-UHFFFAOYSA-N N-glycoloyl-neuraminic acid Natural products OCC(O)C(O)C(O)C(NC(=O)CO)C(O)CC(=O)C(O)=O SUHQNCLNRUAGOO-UHFFFAOYSA-N 0.000 description 3
- FDJKUWYYUZCUJX-UHFFFAOYSA-N N-glycolyl-beta-neuraminic acid Natural products OCC(O)C(O)C1OC(O)(C(O)=O)CC(O)C1NC(=O)CO FDJKUWYYUZCUJX-UHFFFAOYSA-N 0.000 description 3
- FDJKUWYYUZCUJX-KVNVFURPSA-N N-glycolylneuraminic acid Chemical compound OC[C@H](O)[C@H](O)[C@@H]1O[C@](O)(C(O)=O)C[C@H](O)[C@H]1NC(=O)CO FDJKUWYYUZCUJX-KVNVFURPSA-N 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 229940072056 alginate Drugs 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 239000000427 antigen Substances 0.000 description 3
- 108091007433 antigens Proteins 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
- SQVRNKJHWKZAKO-UHFFFAOYSA-N beta-N-Acetyl-D-neuraminic acid Natural products CC(=O)NC1C(O)CC(O)(C(O)=O)OC1C(O)C(O)CO SQVRNKJHWKZAKO-UHFFFAOYSA-N 0.000 description 3
- 238000000502 dialysis Methods 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 235000021144 fermentable dietary fiber Nutrition 0.000 description 3
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 3
- 239000013568 food allergen Substances 0.000 description 3
- 239000001963 growth medium Substances 0.000 description 3
- 230000003870 intestinal permeability Effects 0.000 description 3
- 210000000936 intestine Anatomy 0.000 description 3
- 208000002551 irritable bowel syndrome Diseases 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 235000015097 nutrients Nutrition 0.000 description 3
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 3
- 239000002356 single layer Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 3
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 2
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 2
- OXQGTIUCKGYOAA-UHFFFAOYSA-N 2-Ethylbutanoic acid Chemical compound CCC(CC)C(O)=O OXQGTIUCKGYOAA-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 108010076119 Caseins Proteins 0.000 description 2
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 208000004262 Food Hypersensitivity Diseases 0.000 description 2
- 206010016946 Food allergy Diseases 0.000 description 2
- 108090000288 Glycoproteins Proteins 0.000 description 2
- 102000003886 Glycoproteins Human genes 0.000 description 2
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 2
- 208000019637 Infantile Diarrhea Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- IFQSXNOEEPCSLW-DKWTVANSSA-N L-cysteine hydrochloride Chemical compound Cl.SC[C@H](N)C(O)=O IFQSXNOEEPCSLW-DKWTVANSSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- 208000009793 Milk Hypersensitivity Diseases 0.000 description 2
- 201000010859 Milk allergy Diseases 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 239000001888 Peptone Substances 0.000 description 2
- 108010080698 Peptones Proteins 0.000 description 2
- PLXBWHJQWKZRKG-UHFFFAOYSA-N Resazurin Chemical compound C1=CC(=O)C=C2OC3=CC(O)=CC=C3[N+]([O-])=C21 PLXBWHJQWKZRKG-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000000996 additive effect Effects 0.000 description 2
- WQZGKKKJIJFFOK-PHYPRBDBSA-N alpha-D-galactose Chemical compound OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-PHYPRBDBSA-N 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000036528 appetite Effects 0.000 description 2
- 235000019789 appetite Nutrition 0.000 description 2
- PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
- 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 2
- 229940098773 bovine serum albumin Drugs 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 239000005018 casein Substances 0.000 description 2
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 2
- 235000021240 caseins Nutrition 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000013872 defecation Effects 0.000 description 2
- 230000001066 destructive effect Effects 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 235000021323 fish oil Nutrition 0.000 description 2
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 2
- 235000012041 food component Nutrition 0.000 description 2
- 239000005417 food ingredient Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 210000002175 goblet cell Anatomy 0.000 description 2
- 229960002897 heparin Drugs 0.000 description 2
- 229920000669 heparin Polymers 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 235000021125 infant nutrition Nutrition 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002372 labelling Methods 0.000 description 2
- 238000013160 medical therapy Methods 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- -1 n-3) Chemical compound 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 235000019319 peptone Nutrition 0.000 description 2
- 150000003904 phospholipids Chemical group 0.000 description 2
- 235000013406 prebiotics Nutrition 0.000 description 2
- 230000001681 protective effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229960002477 riboflavin Drugs 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229960003495 thiamine Drugs 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 206010070545 Bacterial translocation Diseases 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- GHOKWGTUZJEAQD-UHFFFAOYSA-N Chick antidermatitis factor Natural products OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 description 1
- 208000015943 Coeliac disease Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 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 description 1
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 1
- 206010012444 Dermatitis diaper Diseases 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 208000003105 Diaper Rash Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 229920000855 Fucoidan Polymers 0.000 description 1
- 208000014540 Functional gastrointestinal disease Diseases 0.000 description 1
- 108010068370 Glutens Proteins 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 240000007049 Juglans regia Species 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
- 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 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 239000005913 Maltodextrin Substances 0.000 description 1
- 229920002774 Maltodextrin Polymers 0.000 description 1
- PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
- 108010011756 Milk Proteins Proteins 0.000 description 1
- 102000014171 Milk Proteins Human genes 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- QSLJIVKCVHQPLV-PEMPUTJUSA-N Oxandrin Chemical compound C([C@@H]1CC2)C(=O)OC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@](C)(O)[C@@]2(C)CC1 QSLJIVKCVHQPLV-PEMPUTJUSA-N 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 108010073771 Soybean Proteins Proteins 0.000 description 1
- 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 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 239000006180 TBST buffer Substances 0.000 description 1
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003451 Vitamin B1 Natural products 0.000 description 1
- 229930003779 Vitamin B12 Natural products 0.000 description 1
- 229930003471 Vitamin B2 Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000012084 abdominal surgery Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-BKBMJHBISA-N alpha-D-galacturonic acid Chemical compound O[C@H]1O[C@H](C(O)=O)[C@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-BKBMJHBISA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 235000021120 animal protein Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 230000007375 bacterial translocation Effects 0.000 description 1
- WQZGKKKJIJFFOK-FPRJBGLDSA-N beta-D-galactose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@H]1O WQZGKKKJIJFFOK-FPRJBGLDSA-N 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 229940093761 bile salts Drugs 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229960002685 biotin Drugs 0.000 description 1
- 235000020958 biotin Nutrition 0.000 description 1
- 239000011616 biotin Substances 0.000 description 1
- 201000007637 bowel dysfunction Diseases 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 150000001746 carotenes Chemical class 0.000 description 1
- 235000005473 carotenes Nutrition 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000013553 cell monolayer Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 235000020247 cow milk Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000001739 density measurement Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 235000019152 folic acid Nutrition 0.000 description 1
- 239000011724 folic acid Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 150000002243 furanoses Chemical group 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000002304 glucoses Chemical class 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 150000001261 hydroxy acids Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 150000004001 inositols Chemical class 0.000 description 1
- 230000004673 intestinal mucosal barrier function Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940076522 listerine Drugs 0.000 description 1
- 235000020667 long-chain omega-3 fatty acid Nutrition 0.000 description 1
- 235000010598 long-chain omega-6 fatty acid Nutrition 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 229940035034 maltodextrin Drugs 0.000 description 1
- 239000011572 manganese Substances 0.000 description 1
- 229910052748 manganese Inorganic materials 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229940055726 pantothenic acid Drugs 0.000 description 1
- 235000019161 pantothenic acid Nutrition 0.000 description 1
- 239000011713 pantothenic acid Substances 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 235000013324 preserved food Nutrition 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 1
- 235000008160 pyridoxine Nutrition 0.000 description 1
- 239000011677 pyridoxine Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 235000019710 soybean protein Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000004206 stomach function Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 108010004085 sulfomucin Proteins 0.000 description 1
- 238000006277 sulfonation reaction Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 150000003538 tetroses Chemical class 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-N thioglycolic acid Chemical compound OC(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-N 0.000 description 1
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000005457 triglyceride group Chemical group 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 239000012137 tryptone Substances 0.000 description 1
- 235000021122 unsaturated fatty acids Nutrition 0.000 description 1
- 150000004670 unsaturated fatty acids Chemical class 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- NCYCYZXNIZJOKI-UHFFFAOYSA-N vitamin A aldehyde Natural products O=CC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C NCYCYZXNIZJOKI-UHFFFAOYSA-N 0.000 description 1
- 235000010374 vitamin B1 Nutrition 0.000 description 1
- 239000011691 vitamin B1 Substances 0.000 description 1
- 235000019163 vitamin B12 Nutrition 0.000 description 1
- 239000011715 vitamin B12 Substances 0.000 description 1
- 235000019164 vitamin B2 Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019158 vitamin B6 Nutrition 0.000 description 1
- 239000011726 vitamin B6 Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940011671 vitamin b6 Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
- 238000004073 vulcanization Methods 0.000 description 1
- 235000020234 walnut Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
The invention relates to an improvement of completeness of an intestinal barrier, in particular to a method for exciting the barrier completeness of mammalian by applying a composition containing eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (ARA) and at least two different oligosaccharides to the mammalians.
Description
The application is that application number is 200480043417.0, and the applying date is on June 22nd, 2004, and denomination of invention is divided an application for the Chinese invention patent application of " improvement of completeness of intestinal barrier ".
Technical field
The compositions that the present invention relates to improve the method for completeness of intestinal barrier and be applicable to the method.
Background technology
Gastrointestinal epithelial serves as the selectivity barrier usually---and it allows to absorb nutrient, electrolyte and water and prevent to be exposed to diet and microbial antigen, comprises food allergen.The gastrointestinal epithelial limited antigen enters in the body circulation, and the latter can cause inflammatory reaction, for example anaphylaxis.Because irritated, particularly the incidence rate of food anaphylaxis grows with each passing day, (preventative) treatment of these diseases is all being sought by many research institutions.
EP1272058 has described and has been used to improve tight connection to reduce the intestinal permeability and to reduce the anaphylactoid compositions that comprises non-fermentable dietary fibers.Said composition can comprise LC-PUFA ' s (long-chain-poly-unsaturated fatty acid).
EP 745001 has described non-fermentable dietary fibers and n-3 and n-6 fatty acid in conjunction with being used for the treatment of ulcerative colitis.
(Clinical Nutrition 2001,20 (4): 351-359) described eicosapentaenoic acid (EPA) to closely connecting infiltrative influence in the intestinal cell monolayer for people such as Usami.In their research, EPA it is found that and improved permeability, this means that EPA is not suitable for improving completeness of intestinal barrier.
The prior art preparation is not to be suitable for improving barrier integrity most.
Summary of the invention
Summary of the invention
The combination of the oligosaccharide that the invention provides the poly-unsaturated fatty acid of selected long-chain (LC-PUFA ' s) and select.The combination of LC-PUFA ' s of the present invention and oligosaccharide improves intestinal permeability and mucus generation and has effectively improved barrier integrity by collaborative, and is particularly suitable for improving the barrier integrity of human infant.
Be surprised to find that selected LC-PUFA ' s effectively reduces the other permeability of epithelial cell.With people (Clinical Nutrition 2001 such as Usami, 20 (4): that 351-359) has discussed is opposite, the inventor finds, C18 and C20 gather unsaturated fatty acid, particularly eicosapentaenoic acid (EPA), docosahexenoic acid (DHA) and arachidonic acid (ARA) can effectively be reduced intestinal and closely be connected permeability.
Except LC-PUFAs, this compositions also comprises oligosaccharide.Selected oligosaccharide has improved barrier integrity by stimulating mucus to generate, and this has improved rete malpighii thickness.This effect is considered to be caused by the influence that different oligosaccharide generate short-chain fatty acid (SCFA).Therefore, when being administered to mammal through intestinal and going up, the combination of LC-PUFA of the present invention and non-fermentable dietary fibers closely is connected permeability and stimulates mucus to generate by reducing simultaneously, works in coordination with to have improved barrier integrity and/or work in coordination with and reduced the intestinal permeability.
Aspect further, this compositions has been improved the quality of casing slime layer.Rete malpighii comprises mucin.Mucin is the high molecular glycoprotein by the synthetic justacrine of goblet cell.They form the gel layer on mucomembranous surface, improve barrier integrity thus.Rete malpighii comprises dissimilar mucin, for example acid, neutrality and sulfonation mucin.The heterogeneity of the raising of rete malpighii is considered to improve barrier function.
This compositions preferably comprises at least two kinds of different oligosaccharide, and they directly or by changing intestinal flora influence the mucin heterogeneity that the mucosa structure also advantageously influences rete malpighii.Every kind of different selected oligosaccharide is considered to that mucus amount and quality are had Different Effects.In addition, two kinds of different oligosaccharide can also promote the mucus quality that embodies as state of cure (vulcanization) by they collaborative generations that stimulates SCFA.The inventor is surprised to find that the mixture of two kinds of different oligosaccharide of the present invention is worked in coordination with has stimulated the acetate generation.The inventor finds that also mucus generates and depends on that acetate generates.
Preferably by providing long-chain and short chain oligosaccharide further to improve this compositions.Provide different chain length to cause stimulating mucus to generate at the different parts of ileum and colon.Short chain oligosaccharide (having 2,3,4 or 5 the degree of polymerization (DP) usually) stimulates mucus to generate in proximal colonic and/or far-end ileum place, and the oligosaccharide that has than long-chain long (preferably having the degree of polymerization (DP) greater than 5 to 60) is considered to stimulate mucus to generate at the more distal site of colon.
By at least two kinds of different oligosaccharide are provided---short chain and long-chain oligosaccharide, can realize further improving.These preferred embodiments all help further to improve the barrier integrity in whole ileum and/or the colon.
In addition, be surprised to find that EPA, DHA and ARA can reduce interleukin-4 (IL-4) to the infiltrative adverse effect of intestinal.IL-4 is excretory and bring out the infiltrative cytokine of intestinal with the amount that improves by mucosa T-cell in some patient's body.Therefore, the present invention also provides the method that improves diseases associated (for example anaphylaxis, particularly atopic dermatitis) with intestinal IL-4 concentration that treats and/or prevents.
Detailed Description Of The Invention
The present invention relates to alimentation composition, it comprises:
A) EPA, DHA and ARA, the content that wherein contains the poly-unsaturated fatty acid of long-chain of 20 and 22 carbon atoms is no more than the 15wt% of total lipid content; With
B) at least two kinds of different oligosaccharide, wherein these two kinds of different oligosaccharide have and are lower than 90% monosaccharide unit homology.
This compositions can be advantageously utilised in the method that excites completeness of intestinal barrier, and described method comprises the described compositions of administration.
Poly-unsaturated fatty acid
The inventor is surprised to find that, eicosapentaenoic acid (EPA, n-3), docosahexenoic acid (DHA, n-3) and arachidonic acid (ARA n-6) effectively reduces intestinal and closely connects permeability.Therefore, this compositions that is particularly suitable for improving completeness of intestinal barrier comprises EPA, DHA and ARA.
The inventor finds that the LC-PUFA ' s of low concentration can effectively reduce tight connection permeability (referring to people such as embodiment vs.Usami).Therefore, the content of LC-PUFA in this compositions that contains 20 and 22 carbon atoms preferably is no more than the 15wt% of total lipid content, preferably is no more than the 10wt% of total lipid content, preferably is no more than 5wt% again.Preferably, compositions of the present invention comprises the 0.1wt% at least that accounts for total lipid content, preferred 0.25wt% at least, more preferably 0.5wt% at least, the preferred again LC-PUFA that contains 20 and 22 carbon atoms of 0.75wt% at least.For the same reason, EPA content preferably is no more than the 5wt% of total fat, more preferably no more than 1wt%, but is preferably the 0.05wt% at least of total fat, more preferably 0.1wt% at least.DHA content preferably is no more than the 5wt% of total fat, more preferably no more than 1wt%, but is at least 0.1wt%.Because ARA it is found that and reduced tight connection permeability especially effectively, this compositions comprises relative higher amount, is preferably the 0.1wt% at least of total fat, preferred 0.25wt% at least again, most preferably 0.5wt% at least.ARA content preferably is no more than the 5wt% of total fat, more preferably no more than 1wt%.Of the present invention contain ARA in the intestinal compositions, advantageously add EPA and DHA effect with balance ARA, for example reduce the metabolic potential short inflammatory effects of ARA.The excess metabolism thing of ARA may cause inflammation.Therefore, this compositions preferably comprises ARA, EPA and DHA, and wherein wt preferably is higher than 0.25 than ARA/DHA, preferably is higher than 0.5, more preferably is higher than 1.This ratio preferably is lower than 25.Weight ratio ARA/EPA is preferably 1 to 100, and more preferably 5 to 20.
This compositions preferably comprise account for total fat 5 to 75wt%, preferred 10 to 50wt% poly-unsaturated fatty acid.
If this compositions is as the infant formula (method of feeding infant for example, described method comprises to this compositions of infant feeding), LU-PUFA, the content that particularly contains the LC-PUFA of 20 and 22 carbon atoms preferably is no more than the 3wt% of total lipid content, because need as far as possible closely to simulate human milk.For the same reason, Ω-3 LC-PUFA content preferably is no more than the 1wt% of total lipid content; Ω-6 LC-PUFA content preferably is no more than the 2wt% of total lipid content; ARA (Ω-6) content preferably is lower than the 1wt% of total lipid content; And/or weight ratio EPA/DHA is preferably 1 or lower, is more preferably less than 0.5.
The LC-PUFA that contains 20 and 22 carbon atoms can be used as free fatty, with the triglyceride form, provide with phospholipid form or as the mixture of one or more above-mentioned forms.This compositions preferably comprises the ARA and the DHA of at least a phospholipid form.
This alimentation composition preferably also provides Ω-9 (n-9) fatty acid (preferred oleic acid, 18: 1), so that enough nutrition to be provided.Preferably, this compositions provides the n-9 fatty acid of the 15wt% at least that accounts for total fatty acids weight, more preferably 25wt% at least.The content of n-9 fatty acid preferably is lower than 80wt%.
Oligosaccharide
Suitable oligosaccharide of the present invention is the saccharide of the degree of polymerization (DP) with at least 2 monosaccharide units, it can or only partly not digest by the acid of existence in the human upper digestive tract (small intestinal stomach function regulating) or the enteral that acts on of digestive enzyme, but it can be fermented by human intestinal flora.The term monosaccharide unit is meant the unit with closed-loop structure, preferred hexose, for example pyranose or furanose form.The degree of polymerization of oligosaccharide is usually less than 60 monosaccharide units, preferably is lower than 40, preferably is lower than 20 again.
This compositions comprises at least two kinds of different oligosaccharide, and wherein oligosaccharide has and is lower than approximately 90%, preferably is lower than 50%, preferably is lower than 25% again, preferably is lower than 5% monosaccharide unit homology again.The term that uses among the present invention " homology " is the percentage ratio accumulation of identical monosaccharide unit in the different oligosaccharide.For example, oligosaccharide 1 (OL1) has structure fructose (fruc)-fructose (fruct)-glucose (glu)-galactose (gal), and comprises 50% fructose thus, 25% galactose and 25% glucose.Oligosaccharide 2 (OL2) has structure fructose-fructose-glucose, and comprises 66% fructose thus, 33% glucose.Therefore different oligosaccharide has 75% homology (50% fructose+25% glucose).
In preferred embodiments, this compositions comprises oligomeric galactose and is selected from least a of oligofructose and inulin.
This oligosaccharide preferably comprises at least 66% separately, and more preferably at least 90% (calculating on the basis of contained therein monosaccharide unit total amount) is selected from the monosaccharide unit of mannose, arabinose, fructose, fucose, rhamnose, galactose, β-D-galactopyranose, ribose, glucose, xylose, alduronic acid and derivant thereof.
According to further embodiment, at least a oligosaccharide of this compositions is selected from levan, oligofructose, difficult digestion dextrin oligomeric galactose (comprising transgalactooligosac,harides), oligomeric xylose, oligomeric arabinose, oligomeric glucose, Oligomeric manna sugar, oligomeric fucose, acidic oligomer sugar and (sees below, for example uronic acid oligosaccharides, for example pectin hydrolysate) and their mixture.Preferably, this compositions comprises at least a, preferred at least two kinds of oligosaccharide that are selected from oligofructose or inulin, oligomeric galactose and pectin hydrolysate.
For good mucus amount and quality, this compositions preferably comprises at least a oligosaccharide that comprises at least 66% galactose or fructose as monosaccharide unit.In preferred embodiments, said composition comprises at least a oligosaccharide and at least a oligosaccharide that comprises at least 66% fructose as monosaccharide unit that comprises at least 66% galactose as monosaccharide unit.In particularly preferred embodiments, this compositions comprises galactooligosacchariwith and the oligosaccharide that is selected from oligofructose and inulin.Oligofructose generates people (2003) Brit J Nutr 89:597-606 such as () Kleessen at the far-end colon moderate stimulation sulfomucin of the relevant rat of human flora, oligomeric galactose has stimulated sour mucin to generate (people such as Meslin, Brit.J.Nutr (1993), 69:903-912).
In order further to improve the thickness of rete malpighii on the whole colon regions, in this compositions at least the oligosaccharide of 10wt% have 2 to 5 DP (promptly 2,3,4 and/or 5), and 5wt% has 10 to 60 DP at least.Preferably, at least 50wt%, more preferably the oligosaccharide of 75wt% has 2 to 9 (promptly at least, 2, DP 3,4,5,6,7,8 and/or 9), because these are considered to play a role at whole ileum with in the near-end and the middle part of colon, and reduced to realizing that required effect need incorporate the percentage by weight of the oligosaccharide in the compositions into.
Preferred weight ratio:
A. (DP is 2 to 5 oligosaccharide): (DP is 6,7,8 and/or 9 oligosaccharide)>1; With
B. (DP is 10 to 60 oligosaccharide): (DP is 6,7,8 and/or 9 oligosaccharide)>1,
Both are all greater than 1.
Preferred two kinds of weight ratios are all greater than 2, more preferably all greater than 5.
In order further to improve rete malpighii thickness and the quality on the whole colon regions, preferably provide at least two kinds of different oligosaccharide with different chain length, based on the gross weight of oligosaccharide separately, the preferred 10wt% at least of every kind of oligosaccharide has 2 to 5 DP (promptly, 2,3,4 and/or 5), and at least 5wt% has 10 to 60 DP.Based on this oligosaccharide gross weight, the preferably 50wt% at least of this oligosaccharide, more preferably 75wt% has 2 to 10 DP at least, because these are considered to play a role at whole ileum with in the near-end and the middle part of colon.
Acidic oligomer sugar
In order further to improve barrier integrity, it is 2 to 60 acidic oligomer sugar that this compositions preferably includes DP.Term acidic oligomer sugar is meant and comprises the oligosaccharide that at least one is selected from the acidic group of N-acetyl neuraminic acid, N-glycolyl neuraminic acid, free or esterification carboxylic acid, sulfate group and phosphate group.Acidic oligomer sugar preferably comprises uronic acid unit (being uronic acid polymer), more preferably galacturonic acid acid unit.Acidic oligomer sugar can be homogenizing or heterogeneous carbohydrate.Suitable example is the hydrolyzate of pectin and/or alginate.In intestinal, uronic acid polymer is hydrolyzed into the alduronic acid monomer, this has stimulated the generation of enteral acetate, its stimulated again the casing slime secretion (people such as Barcelo, Gut 2000; 46:218-224).
Preferably, acidic oligomer sugar has following structure I, and wherein terminal hexose (left side) preferably comprises two keys.Hexose beyond the terminal hexose units is preferably uronic acid unit, more preferably the galacturonic acid acid unit.Hydroxy-acid group on these unit can be for free or (part) esterification, and preferred at least 10% methylate (seeing below).
Structure I: polymerizable acidic oligosaccharide
Wherein:
R is preferably selected from hydrogen, hydroxyl or acidic group, preferred hydroxyl; And
R
2, R
3, R
4And R
5In at least one represent N-acetyl neuraminic acid, N-glycolyl neuraminic acid, free or esterification carboxylic acid, sulfate group and phosphate group, and R
2, R
3, R
4And R
5In all the other group representation hydroxy and/or hydrogen.Preferably, R
2, R
3, R
4And R
5In one represent N-acetyl neuraminic acid, N-glycolyl neuraminic acid, free or esterification carboxylic acid, sulfate group or phosphate group, and all the other group representation hydroxy and/or hydrogen.More preferably, R
2, R
3, R
4And R
5In a free or esterification carboxylic acid of representative, and R
2, R
3, R
4And R
5In all the other group representation hydroxy and/or hydrogen; And
N is integer and is meant hexose number (degree of polymerization also vide infra) that it can be any hexose.Suitably, n is the integer of 1-5000.Preferably, hexose is a uronic acid unit.
Most preferably, R
1, R
2And R
3Representation hydroxy, R
4Represent hydrogen, R
5Represent carboxylic acid, n is 1 to 250, any number of preferred 1 to 10, and hexose is a galacturonic acid.
Detection, measurement and the analysis of the preferred acidic oligosaccharide that uses in this method provides in the patent application formerly (being WO 0/160378) of applicant about acidic oligomer sugar.
Stimulation for rete malpighii thickness on the whole colon regions improves, this compositions preferably comprise the acidic oligomer sugar of (promptly 2,3,4 and/or 5) that is 2 to 5 of 10wt%DP at least and at least 5wt%DP be 10 to 60 acidic oligomer sugar, described wt% is based on the gross weight of oligosaccharide.
Acidic oligomer sugar used among the present invention is more preferably made by pectin and/or alginate preferably by pectin, pectate, alginate, chrondroitin, hyaluronic acid, heparin, heparin (heparane), antibacterial carbohydrate, sialic saccharide (sialoglycans), fucoidan, oligomeric fucose (fucooligosaccharides) or carrageenin.
Oligosaccharide content
When in instant liquid form, this compositions comprises 0.1 to 100 gram indigestible oligosaccharide for preferred every liter, more preferably every liter 0.5 to 50 gram, preferred more every liter 1 to 25 gram.Too high oligosaccharide content may cause discomfort owing to excessive fermentation, and low-down content may cause the rete malpighii deficiency.
The weight ratio of at least two kinds of different oligosaccharide is preferably 1 to 10, and more preferably 1 to 5.The dissimilar diverse location of mucin in intestinal of the most suitable stimulation of these weight ratios generates.
Preferably comprise the 0.1wt% that surpasses that accounts for the compositions gross dry weight in of the present invention the compositions, preferably surpass 0.2wt%, more preferably surpass 0.5wt%, preferably surpass the oligosaccharide of 1wt% again.This compositions preferably has the 20wt% of being lower than, and more preferably less than 10wt%, preferably is lower than the oligosaccharide content of 5wt% again.
In this compositions, add nucleotide and/or nucleoside and further improved the intestinal mucosal barrier function, particularly because its inhibition and/or reduced the incidence rate of bacterial translocation and reduced damage of intestines.Therefore, also preferred per 100 grams of this compositions are done to fill a prescription and are comprised 1 to 500 milligram of nucleoside and/or nucleotide, more preferably 5 to 100 milligrams.
Use
This compositions can be advantageously utilised in improves mammal, in the method for the interior barrier integrity of particularly human body.This compositions also can be advantageously utilised in the treatment or prevention method with the barrier integrity diseases associated that reduces, and described method comprises this compositions of administration.This compositions preferred oral.
For patient and baby, this compositions preferably combines with complete nutrition (comprising protein, carbohydrate and fat).This compositions is advantageously used in 0 to 2 years old big baby.Said composition can be used for impaired patient of barrier integrity and healthy patients.This compositions is advantageously utilised in the method for the nutritional need that premature infant (baby of birth before the conceived expiration of 37 weeks) is provided.
This compositions also can be advantageously utilised in the method that treats and/or prevents damage of intestines by before or after the medical therapy that may cause damage of intestines the patient being used this compositions.This medical therapy can be, for example, and surgery or through intestinal Drug therapy (for example antibiotic, analgesic, NSAID, chemotherapeutant, or the like).
This compositions also can be advantageously used in treatment or prevent following disease---and its midgut barrier destroys the basis that constitutes this disease process development, for example be used in the method for treatment or prophylaxis of chronic, particularly inflammatory bowel (IBD), irritable bowel syndrome (IBS), celiac disease, pancreatitis, hepatitis, arthritis or diabetes.In addition, the present invention also can be used on to or carry out the patient of abdominal surgery and postoperative bowel dysfunction patient and/or malnutrition patient and provide in the method for nutrition.
In further embodiment of the present invention, this compositions is advantageously used in acquired immune deficiency syndrome (AIDS) (AIDS) patient and/or infects the patient of HIV (human immunodeficiency virus) (HIV), for example, is used in the method for treatment AIDS and/or HIV infection.Described method comprises oral compositions, preferably combines with the nutrient that is selected from carbohydrate, protein and fat.
In addition, the complication that the present invention also can be used for treating or prevents to be caused by the barrier integrity that reduces particularly is used in and treats and/or prevents diarrhoea, particularly in the method for infantile diarrhea.Because the reduction of infantile diarrhea incidence rate, this compositions also can be advantageously used in the reduction diaper rash.
Use this compositions and reduced diet and microbial antigen, particularly food allergen enters mucosa or the body circulation from enteric cavity, and therefore can be advantageously utilised in treatment or Polyglucan disease and/or the anaphylactoid method, particularly be used in treatment or prevention phagopyrism, for example in the anaphylactoid method that causes by food intake.
The inventor finds that also EPA, DHA and/or ARA can reduce IL-4 to the infiltrative influence of intestinal.Therefore, one aspect of the present invention provides the method that treats and/or prevents that improves diseases associated (for example anaphylaxis) with intestinal IL-4 concentration, described method comprises using and is preferably selected from EPA, DHA and ARA, preferably with the bonded LC-PUFA of the selected oligosaccharide of the present invention.Therefore, the present invention also can be advantageously utilised in the method for treatment atopic dermatitis.
Because neonatal barrier function is not completed into as yet, this compositions can be advantageously used in young infant, promptly 0 to 6 months big babies.Said composition can be used for the baby with no human milk or with the blended infant formula form of human milk.Therefore, the present invention also provides the formulations that comprises human milk and this compositions.The compositions that comprises human milk and this compositions is specially adapted to feeding premature babies.
This compositions preferably provides as packing powder or packaged instant prescription.In order to prevent damage of product, the Package size of instant prescription preferably is no more than once gives appetite, for example, preferably is no more than 500 milliliters; The Package size of this compositions of powder type preferably is no more than 250 times and gives appetite.The suitable package of powder is of a size of 2000 grams or lower, is preferably 1000 grams or lower.
Have clearly or implicitly indicate consumer according to one or more above-mentioned or following purpose use the packaging product of the label of described product to comprise in the present invention.This label can for example be quoted the anaphylactoid method of prevention of the present invention to food allergen by the wording or the similar wording that comprise " food sensitivity of reduction ", " improving the intestinal toleration ", " improved food toleration " and so on.Similarly, can quote the hypersensitive method that treats and/or prevents of the present invention by comprising the term suitable with " improved repellence " or " sensitivity of reduction ".
Preparation
This compositions it is found that and can be advantageously used in food, for example in pablum and the clinical food.This food preferably comprises lipid, protein and carbohydrate, and preferably uses with liquid form.Term used herein " supping " comprises dry food (for example powder), described dried foods mixture can be mixed with suitable liquid (for example water) according to description.
Therefore, the invention still further relates to and preferably comprise 5 to 50en% lipids, 5 to 50en% protein, the alimentation composition of the combination of 15 to 90en% carbohydrates and oligosaccharide of the present invention and LC-PUFA ' s.Preferably, this alimentation composition preferably comprises 10 to 30en% lipids, 7.5 to 40en% protein and 25 to 75en% carbohydrates (en% is the abbreviation of energy percentage, represents the Relative Contribution amount of every kind of composition to the goods gross calorific value).
Preferably, use vegetable lipid and at least a combination that is selected from fish oil and Ω-3 plant, algae or antibacterial oil.
Used protein is preferably selected from inhuman animal protein (for example lactoprotein, meat albumen and egg albumen), phytoprotein (for example soybean protein, glutelin, rice protein and Semen Pisi sativi protein), free amino acid and their mixture in this dietetic product.The cow's milk protein of Lac Bovis seu Bubali deutero-nitrogenous source, particularly casein and lactalbumin and so on is preferred especially.
Can in nutrient formulation, add the digestible carbohydrate source.It preferably provides about 40% to about 80% energy of alimentation composition.Can use any suitable carbohydrate (source), for example sucrose, lactose, glucose, fructose, corn-syrup solids and maltodextrin and their mixture.
This compositions is preferably used as infant formula and is also preferably comprised 7.5 to 12.5 energy % protein; 40 to 55 energy % carbohydrates; With 35 to 50 energy % fat.Because this compositions is applicable to the anaphylaxis that reduces the baby, the protein of infant formula is preferably selected from lactoalbumin hydrolysate (for example caseinhydrolysate or lact albumin hydrolysate), vegetable protein and/or aminoacid.These proteinic uses have further reduced baby's anaphylaxis.
Irregular defecation (for example, feces is stiff, just quantity not sufficient, diarrhoea) is the patient's of many babies of puzzlement and edible supping a major issue.Discovery can more preferably be used oligosaccharide of the present invention and alleviate the defecation problem by having 50 to 500mOsm/kg in the supping of 100 to 400mOsm/kg osmolality.
Consider the problems referred to above, important also comprises, supping does not have undue heat density but still the heat that is enough to support object is provided.Therefore, supping preferably has the heat density of 0.1 to 2.5 kcal/ml, more preferably the heat density of 0.5 to 1.5 kcal/ml, the most preferably heat density of 0.6 to 0.8 kcal/ml.
Description of drawings
Fig. 1 has shown time and dosage (10 μ Ms and 100 μ Ms) the dependency effect of various fatty acids (Palmic acid, DHA, GLA and AA) to basic barrier integrity (TER).
Fig. 2 has shown that various FA ' s (Palmic acid, DHA, GLA and ARA) destroy the time and dosage (10 μ M and 100 μ M) the dependency protective effect of (flux) to the barrier of IL-4 mediation.
Fig. 3 described to make different oligosaccharide fermentations and absolute (Fig. 3 A) scheme (Fig. 3 B) with relative SCFA.
Fig. 4 has shown the influence that SCFA (acetate, propionate, butyrate) expresses MUC-2 in enterocyte (MCT84) and epithelium mesenchymal cell coculture (CC T84).
The specific embodiment
Embodiment
Embodiment 1:LC-PUFA is to the influence of barrier integrity
With monolayer (MC) enterocyte is T84 (American Type Culture Collection (ATTC), Manassas, the U.S.) go up cultivation at the transwell filter (Corning, Costar BV, Holland) that can carry out sampling of mucosa and serous coat and stimulating human enterocyte.Converge two weeks of back, these monolayers are used poly-unsaturated fatty acid ARA (arachidonic acid in chamber (luminal compartment); 5,8,11,14-eicosatetraenoic acid), DHA (cis-4,7,10,13,16,19 docosahexenoic acid), EPA (eicosapentaenoic acid) or tester Petiolus Trachycarpi (C 16:0) acid (Palm) (Sigma, St.Louis, U.S.) cultivates.The program of selecting the latter is with route of administration in the body of simulation diet chemical compound.Cell was cultivated 0,24,48 and 72 hour with variable concentrations (10 μ M and 100 μ M) with ARA, DHA, EPA or Palmic acid.Experimentize to evaluate and test basis (basal) barrier integrity.By using epithelium voltage resistance meter (EVOM; World Precision Instruments, Germany) record transepithelial electrical resistance (TER, Ω .cm
2) and the permeability of 4kD FITC glucosan (the other permeability labelling of cell, Sigma, the U.S.), determine the epithelium barrier function.Following mensuration resistance (the epithelium permeability of 4kDa FITC glucosan).Flow out (fluxes) before at glucosan, culture medium with not containing phenol red culture media supplemented 1 hour, is added 5 microlitres (reserves 100 mg/ml) 4kDa FITC glucosan then in chamber (lumenal compartment).After 30 minutes cultivate, from the serous coat compartment, collect 100 microlitre samples and measure fluorescence signal (FLUOstar with 485 nanometer excitation wavelengths and 520 nanometer emission wavelengths
BMG Labtechnologies, the U.S.).With pmolFITC-glucosan/square centimeter/hour calculating FITC-glucosan flux.Use ANOVA (SPSS version 10) to carry out statistical analysis.
After cultivating 72 hours, fatty acid (100 μ M) is listed in the table 1 influence of spontaneous barrier integrity.Table 1 shows that LU-PUFA ' s ARA, EPA and DHA have reduced molecular flux and improved epithelium resistance.On the contrary, control experiment shows that Palmic acid has adverse effect, has promptly damaged barrier integrity.These results show, EPA, DHA and ARA, particularly ARA in compositions of the present invention favourable purposes and in method of the present invention, the purposes in the method for improving barrier integrity for example.These results further prove the cooperative effect of the combination of fatty acid of the present invention and indigestible oligosaccharide.
Fig. 1 has shown time and dosage (10 μ Ms and 100 μ Ms) the dependency effect of various fatty acids (Palmic acid, DHA, GLA and AA) to basic barrier integrity (TER).Fig. 1 shows that shown in the resistance (TER) that improves, LC-PUFA ' s AA, DHA and GLA have improved the epithelium barrier integrity.These results show EPA, DHA, GLA and ARA, particularly ARA in compositions of the present invention favourable purposes and in method of the present invention, the purposes in improving the method for barrier integrity for example.These results further prove the cooperative effect of the combination of fatty acid of the present invention and indigestible oligosaccharide.
Table 1
? Composition (LC-PUFA) | ?? Flux | ? Resistance (TER) |
Tester | ??79 | ?1090 |
Palmic acid | ??161 | ?831 |
?DHA | ??72 | ?1574 |
?ARA | ??28 | ?1816 |
?EPA | ??65 | ?1493 |
Embodiment 2:LC-PUFA is to the destructive influence of barrier of IL-4 mediation
With monolayer (MC) enterocyte is that T84 (ATTC, the U.S.) goes up cultivation at the transwell filter (Corning, CostarBV, Holland) that can carry out sampling of mucosa and serous coat and stimulating human enterocyte.Converge the back two weeks, with these monolayers at IL-4 (2 nanograms/milliliter, serous coat compartment, Sigma, U.S.) exist down and containing or do not containing poly-unsaturated fatty acid ARA, DHA, GLA, EPA or contrast Palmic acid (10 μ M or 100 μ M, mucosa compartment, Sigma, St.Louis, the U.S.) situation under cultivate.Before IL-4 cultivates, cell was cultivated 48 hours with ARA, DHA, EPA or Palmic acid are pre-.The common cultivation of PUFA ' s and Palmic acid and IL-4 continues 48 hours again; Changed culture medium and additive in per 24 hours.Determine the epithelium barrier function by measuring transepithelial electrical resistance (TER) and permeability as described in example 1 above.Add up evaluation and test as described in example 1 above.
ARA, DHA, EPA and Palmic acid (100 μ M) the results are shown in the table 2 the destructive influence of barrier of IL-4 mediation.Table 2 shows that LC-PUFA ' s ARA, DHA and EPA have suppressed the flux raising that IL-4 causes.On the contrary, Palmic acid has adverse effect and compares with tester and reduced barrier destruction.These results show that ARA, DHA and EPA prevent or reduce the favourable purposes of the barrier destruction (destroying as the barrier that takes place) of IL-4 mediation in clinical and infant nutrition prescription in food or milk allergy.These results further prove the cooperative effect of the combination of fatty acid of the present invention and indigestible oligosaccharide.
Fig. 2 has shown that various FA ' s (Palmic acid, DHA, GLA and ARA) destroy the time and dosage (10 μ M and 100 μ M) the dependency protective effect of (flux) to the barrier of IL-4 mediation.Fig. 2 shows that shown in the 4kD glucosan flux that reduces, the barrier that ARA, DHA and GLA have suppressed the IL-4 mediation destroys.These results show that ARA, DHA and EPA prevent or reduce the favourable purposes of the barrier destruction (destroying as the barrier that takes place) of IL-4 mediation in clinical and infant nutrition prescription in food or milk allergy.These results further prove the cooperative effect of the combination of fatty acid of the present invention and indigestible oligosaccharide.
Table 2
? Composition (LC-PUFA) | ?? The IL-4 flux | ?? IL-4TER |
Tester | ??582 | ??374 |
Palmic acid | ??777 | ??321 |
?DHA | ??271 | ??547 |
?ARA | ??218 | ??636 |
?EPA | ??228 | ??539 |
Embodiment 3: the influence that oligosaccharide generates acetate
Microorganism is available from the baby's of bottle feeding fresh excreta.To compile from 1 to 4 months big babies' fresh excreta material and in anticorrosion medium, place 2 hours.As substrate, use prebiotics (TOS); TOS/ inulin (HP) mixture of 9/1 (w/w) ratio; Inulin; Oligofructose (the OS)/inulin mixture of 1/1 (w/w) ratio, or what does not use (blank).Transgalactooligosac,harides (TOS) is available from Vivinal GOS, Borculo DomoIngredients, Zwolle, Holland, and comprise 33wt% disaccharide, 39wt% trisaccharide, 18wt% tetrose, 7wt% pentasaccharides and 3wt% six-, seven-en, eight sugar be as indigestible oligosaccharide.Inulin (HP) Orafti Active Food Ingredients, Tienen, Belgium, i.e. Raftiline
Has 23 average DP.Medium: McBain﹠amp; Macfarlane medium: buffering peptone water 3.0 grams per liters, yeast extract 2.5 grams per liters, mucin (brush border) 0.8 grams per liter, tryptone 3.0 grams per liters, L-cysteine-HCl 0.4 grams per liter, bile salts 0.05 grams per liter, K
2HPO
4.3H
2O 2.6 grams per liters, NaHCO
30.2 grams per liter, NaCl 4.5 grams per liters, MgSO
4.7H
2O 0.5 grams per liter, CaCl
20.228 grams per liter, FeSO
4.7H
2O 0.005 grams per liter.The medium of in 500 milliliters of Scott bottles, packing into, and 121 ℃ of sterilizations 15 minutes.Buffer medium: K
2HPO
4.3H
2O 2.6 grams per liters, NaHCO
30.2 grams per liter, NaCl 4.5 grams per liters, MgSO
4.7H
2O 0.5 grams per liter, CaCl
20.228 grams per liter, FeSO
4.7H
2O 0.005 grams per liter.Use K
2HPO
4Or NaHCO
3Be adjusted to pH 6.3 ± 0.1.The medium of in 500 milliliters of Scott bottles, packing into, and 121 ℃ of sterilizations 15 minutes.
Anticorrosion medium: buffering peptone water 20.0 grams per liters, L-cysteine-HCl 0.5 grams per liter, THIOGLYCOLLIC ACID are received 1/ liter of salt 0.5 grams per liter, "diazoresorcinol" (resazurine) sheet, are adjusted to pH 6.7 ± 0.1 with 1M NaOH or HCl.In microwave, seethe with excitement.25 mL media of in serum bottle, packing into and 121 ℃ the sterilization 15 minutes.
Fresh excreta sample and anticorrosion medium mixed be incorporated in 4 ℃ and preserve a few hours.With 13, centrifugal 15 minutes of 000rpm removes supernatant with the listerine of feces, and with feces and McBain﹠amp; Mac Farlane medium mixes with 1: 5 weight ratio.With 3 milliliters of this feces suspensions in bottle with 85 milligrams of glucoses or prebiotics or do not merge and fully mix with any additive (blank).When t=0, extract sample (0.5 milliliter).2.5 milliliters of gained suspensions are introduced in the dialysis tube in 60 milliliters of bottles that 60 milliliters of buffer mediums are housed.Should bottle fully sealing and 37 ℃ of cultivations.Extracted sample with hypodermic syringe from dialysis tube (0.2 milliliter) or dialysis buffer agent (1.0 milliliters) after 3,24 and 48 hours, existing side by side soon, it places on ice to stop fermentation.Use following sample to experimentize:
1) 85 milligrams of TOS
2) 85 milligrams of inulin
3) 85 milligrams of ratios TOS/ inulin that is 9/1 (w/w) and
4) 85 milligrams of OS/ inulin that ratio is 1/1 (w/w).
Use is furnished with the amount of Varian 3800 gas chromatograies (GC) (VarianInc., Walnut Creek, the U.S.) the mensuration SCFA (acetate, propionate, butyrate) of flame ionisation detector.Use helium to do carrier gas (3.0psi), in post (Stabilwax, 15 * 0.53 millimeters, 1.00 microns of thickness, Restek Co., the U.S. .), inject 0.5 microlitre sample at 80 ℃.After the injected sample, this stove is heated to 160 ℃ with 16 ℃/minute speed, is heated to 220 ℃ with 20 ℃/minute speed then, kept 1.5 minutes at 220 ℃ at last.The temperature of syringe and detector is 200 ℃.Use 2 Ethylbutanoic acid to make interior mark.
Fig. 3 described to make different oligosaccharide fermentations and absolute (Fig. 3 A) scheme (Fig. 3 B) with relative SCFA.Fig. 3 A shows, the mixture of two kinds of different oligosaccharide (TOS/ inulin) (wherein two kinds of different oligosaccharide have the monosaccharide unit homology and different chain lengths less than 90) causes comparing obviously and the amount of the SCFA (particularly acetate) of the every gram fiber that improves synergistically with individual components.Fig. 3 B shows that the compositions of adding the TOS/ inulin helps producing more a high proportion of useful acetate (B).Acetate output becomes in live body by the mucus output of goblet cell raising and a kind of measurement standard (referring to embodiment 4) of casing slime layer thickness.These results show the favourable purposes of this compositions.
The influence that embodiment 4:SCFA generates mucus
Monolayer enteric epithelium T84 cell (ATTC, the U.S.) is cultivated in 24 or 96 hole tissue culturing plates (Corning B.V.).T84 was cultivated 24 hours with the concentration range of 0.025-4.0mM with short-chain fatty acid acetate, propionate and butyrate (SCFA, Merck, the U.S.).Collect supernatant and/or cell and measure the expression of MUC-2 (mucin).Use the MUC-2 in the dot blotting technical measurement cell culture to express, because mucin is great glycoprotein (surpassing 500kDa), this makes them be difficult to operation in western blotting technique.Use pre-immune serum (T84 dye negative thing), CCD-18Co (ATCC, the U.S.) negative control cell and bovine serum albumin (BSA) to confirm this method.Collecting cell sample and use micro protein checking method (Biorad, the U.S.) to carry out protein determination in Laemmli (Separation of Proteins buffer agent) according to the indication of manufacturer.At NC Nitroncellulose film (Schleicher﹠amp; Schuell, Germany) go up with a labelling sample (0.3-0.7-1.0 microgram/2 microlitres).With film sealing in TBST/5%Protivar (Nutricia, Holland), use then to resist-MUC-2 antibody (Dr.Einerhand, Erasmus University, Rotterdam, Holland grants with open arms) cultivated 1 hour.After the washing, trace is cultivated with goat-anti rabbit-HRP (Santacruz Biotechnolog, the U.S.), detected, use ECL (Roche Diagnostics, Holland) for substrate.Use Lumi-Imager (BoehringerMannheim B.V., Holland) to carry out density measurement also with light unit (BLU) expression signal.Also relatively represent BLU ' s (%BLU) with contrast culture.In order to compare SCFA, deduct basic MUC-2 expression to the excitation that MUC-2 expresses.
Fig. 4 has shown the influence that SCFA (acetate, propionate, butyrate) expresses MUC-2 in enterocyte (MCT84) and epithelium mesenchymal cell coculture (CC T84).Fig. 2 shows that also acetate is compared with butyrate with propionate, and is more effective aspect stimulation MUC-2 expression (mucus generation).Therefore, oligosaccharide combination of the present invention (it shows and has improved acetate output (referring to embodiment 3)) is particularly useful for stimulating mucus to generate and can be advantageously utilised in the method that excites barrier integrity.
Embodiment 5: the baby milk formula I
Composition (every liter), 672 kilocalories of energy; Protein 15 grams; Milk surum: casein ratio 60: 40; Fat 36 grams; Carbohydrate 72 grams; Vitamin A 750 RE; Mix carotene (carotids) 400IU; Vitamin D 10.6 micrograms; 7.4 milligrams of vitaminFs; Vitamin K 67.0 micrograms; Vitamin B1 (thiamine) 1000 micrograms; Vitamin B2 (riboflavin) 1500 micrograms; Vitamin B6 (pyridoxol) 600 micrograms; Vitamin B12 (cyanacobalmine) 2.0 micrograms; Nicotinic acid 9.0 micrograms; Folic acid 80 micrograms; Pantothenic acid 3000 micrograms; Biotin 90 micrograms; 90 milligrams of vitamin Cs (ascorbic acid); 100 milligrams in choline; 33 milligrams of inositols; 460 milligrams of calcium; 333 milligrams in phosphorus; 64 milligrams in magnesium; 8.0 milligrams of ferrum; 6.0 milligrams on zinc; Manganese 50 micrograms; Copper 560 micrograms; Iodine 100 micrograms; 160 milligrams in sodium; 650 milligrams in potassium; 433 milligrams of chlorides and selenium 14 micrograms; Wherein fat content comprises 3 gram fish oil and 3 gram 40% arachidonic oil (DSM Food Specialities, Delft, Holland); Further comprise 4 gram transgalactooligosac,harides acid Elix ' or
TM(Borculo Domo Ingredients, Holland) and 4 gram Raftiline
TM(Orafti Active Food Ingredients, Belgium).
Claims (11)
1. infant formula composition, it comprises the protein of 7.5 to 12.5 energy %; The carbohydrate of 40 to 55 energy %; With the fat of 35 to 50 energy %, wherein said protein comprise lactoprotein, vegetable protein and/or amino acid whose a member of being selected from hydrolysis and
A.EPA, DHA and ARA, the content that wherein contains the poly-unsaturated fatty acid of long-chain of 20 and 22 carbon atoms is no more than the 15wt% of total lipid content; With
B. at least two kinds of different oligosaccharide (OL1 and OL2), wherein these two kinds of different oligosaccharide have and are lower than 90% monosaccharide unit homology; With
C. per 100 grams are done 1 to 500 milligram of nucleoside and/or nucleotide that prescription comprises.
2. compositions according to claim 1, wherein said protein are the lactoprotein of hydrolysis.
3. compositions according to claim 2, wherein said protein are caseinhydrolysate or lact albumin hydrolysate.
4. infant formula composition, it comprises the protein of 7.5 to 12.5 energy %; The fat of the carbohydrate of 40 to 55 energy % and 35 to 50 energy %, wherein said protein be aminoacid and/or vegetable protein and
A.EPA, DHA and ARA, the content that wherein contains the poly-unsaturated fatty acid of long-chain of 20 and 22 carbon atoms is no more than the 15wt% of total lipid content; With
B. at least two kinds of different oligosaccharide (OL1 and OL2), wherein these two kinds of different oligosaccharide have and are lower than 90% monosaccharide unit homology.
5. according to the described compositions of claim 1-4, it comprises oligomeric galactose and the levan that is selected from oligofructose, inulin and composition thereof.
6. according to the described compositions of claim 1-5, wherein at least the oligosaccharide of 10wt% have 2 to 5 the degree of polymerization (DP) and at least 5wt% have 10 to 60 DP.
7. according to each described compositions of claim 1-6, further comprise acidic oligomer sugar, preferred DP is 2 to 60 uronic acid polymer.
8. according to each described compositions of claim 1-7, described compositions has the energy content of 0.6 to 0.8 kcal/ml; 50 to 500mOsm/kg osmolality; With the viscosity that is lower than 50mPas.
9. according to each described compositions of claim 1-8, as medicament.
10. the purposes that is used for 0 to 2 years old baby's compositions according to each described compositions of claim 1-8 in preparation.
11. be used for preparation treatment or Polyglucan disease according to each described compositions of claim 1-8, the purposes of the medicine of particularly treating or preventing to use in the method for phagopyrism, described method comprises administration according to each described compositions of claim 1-8.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200910209324 CN101693103B (en) | 2004-06-22 | 2004-06-22 | Improvement of completeness of intestinal barrier |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN 200910209324 CN101693103B (en) | 2004-06-22 | 2004-06-22 | Improvement of completeness of intestinal barrier |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN200480043417A Division CN100589712C (en) | 2004-06-22 | 2004-06-22 | Improvement of intestinal barrier integrity |
Publications (2)
Publication Number | Publication Date |
---|---|
CN101693103A true CN101693103A (en) | 2010-04-14 |
CN101693103B CN101693103B (en) | 2013-04-10 |
Family
ID=42092130
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN 200910209324 Expired - Lifetime CN101693103B (en) | 2004-06-22 | 2004-06-22 | Improvement of completeness of intestinal barrier |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN101693103B (en) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013053073A1 (en) * | 2011-10-10 | 2013-04-18 | Huang Daiyong | Mannan oligosaccharide-based gastrointestinal tract health factor composition |
CN106793824A (en) * | 2014-10-01 | 2017-05-31 | Mjn 美国控股有限责任公司 | Micropopulation and the alimentation composition of metabolic characteristics that offer for gastroenteric environment improves |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5952314A (en) * | 1994-04-01 | 1999-09-14 | Demichele; Stephen Joseph | Nutritional product for a person having ulcerative colitis |
US6495599B2 (en) * | 2000-04-13 | 2002-12-17 | Abbott Laboratories | Infant formulas containing long-chain polyunsaturated fatty acids and uses therof |
EP1155627A1 (en) * | 2000-05-18 | 2001-11-21 | Belovo Eggs & Egg Products | Eggs with balanced lipid composition |
-
2004
- 2004-06-22 CN CN 200910209324 patent/CN101693103B/en not_active Expired - Lifetime
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2013053073A1 (en) * | 2011-10-10 | 2013-04-18 | Huang Daiyong | Mannan oligosaccharide-based gastrointestinal tract health factor composition |
CN106793824A (en) * | 2014-10-01 | 2017-05-31 | Mjn 美国控股有限责任公司 | Micropopulation and the alimentation composition of metabolic characteristics that offer for gastroenteric environment improves |
Also Published As
Publication number | Publication date |
---|---|
CN101693103B (en) | 2013-04-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN100589712C (en) | Improvement of intestinal barrier integrity | |
CN1972604B (en) | Improvement of barrier integrity in HIV patients | |
CN101360490A (en) | Composition with docosapentaenoic acid | |
CN101693103B (en) | Improvement of completeness of intestinal barrier | |
JP5502817B2 (en) | Improving barrier integrity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
C14 | Grant of patent or utility model | ||
GR01 | Patent grant | ||
CX01 | Expiry of patent term |
Granted publication date: 20130410 |
|
CX01 | Expiry of patent term |