JP6888145B2 - LPS production inhibitor and food composition for suppressing LPS production - Google Patents
LPS production inhibitor and food composition for suppressing LPS production Download PDFInfo
- Publication number
- JP6888145B2 JP6888145B2 JP2020050613A JP2020050613A JP6888145B2 JP 6888145 B2 JP6888145 B2 JP 6888145B2 JP 2020050613 A JP2020050613 A JP 2020050613A JP 2020050613 A JP2020050613 A JP 2020050613A JP 6888145 B2 JP6888145 B2 JP 6888145B2
- Authority
- JP
- Japan
- Prior art keywords
- lps
- blood
- concentration
- extract
- fraction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 235000013305 food Nutrition 0.000 title claims description 62
- 238000004519 manufacturing process Methods 0.000 title claims description 55
- 239000000203 mixture Substances 0.000 title claims description 49
- 239000003112 inhibitor Substances 0.000 title claims description 20
- SUVMJBTUFCVSAD-UHFFFAOYSA-N sulforaphane Chemical compound CS(=O)CCCCN=C=S SUVMJBTUFCVSAD-UHFFFAOYSA-N 0.000 claims description 108
- GMMLNKINDDUDCF-JRWRFYLSSA-N [(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] (1e)-5-[(r)-methylsulfinyl]-n-sulfooxypentanimidothioate Chemical compound C[S@@](=O)CCCC\C(=N/OS(O)(=O)=O)S[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GMMLNKINDDUDCF-JRWRFYLSSA-N 0.000 claims description 82
- RUQCCAGSFPUGSZ-OBWQKADXSA-N Glucoraphanin Natural products C[S@](=O)CCCCC(=NS(=O)(=O)O)S[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RUQCCAGSFPUGSZ-OBWQKADXSA-N 0.000 claims description 79
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 claims description 54
- 235000015487 sulforaphane Nutrition 0.000 claims description 54
- 229960005559 sulforaphane Drugs 0.000 claims description 54
- 239000008280 blood Substances 0.000 claims description 40
- 210000004369 blood Anatomy 0.000 claims description 40
- 239000000284 extract Substances 0.000 claims description 40
- 241000196324 Embryophyta Species 0.000 claims description 33
- 235000011299 Brassica oleracea var botrytis Nutrition 0.000 claims description 28
- 235000017647 Brassica oleracea var italica Nutrition 0.000 claims description 28
- 240000003259 Brassica oleracea var. botrytis Species 0.000 claims description 27
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 239000004480 active ingredient Substances 0.000 claims description 17
- 210000000936 intestine Anatomy 0.000 claims description 10
- 230000007423 decrease Effects 0.000 claims description 9
- 241000219193 Brassicaceae Species 0.000 claims description 5
- 230000001629 suppression Effects 0.000 claims 4
- 239000000463 material Substances 0.000 claims 2
- 239000002158 endotoxin Substances 0.000 description 75
- 229920006008 lipopolysaccharide Polymers 0.000 description 73
- 230000000968 intestinal effect Effects 0.000 description 31
- 238000000034 method Methods 0.000 description 27
- 230000001580 bacterial effect Effects 0.000 description 25
- 241000894006 Bacteria Species 0.000 description 22
- 235000005911 diet Nutrition 0.000 description 22
- 230000037213 diet Effects 0.000 description 22
- 102000052508 Lipopolysaccharide-binding protein Human genes 0.000 description 19
- 108010053632 Lipopolysaccharide-binding protein Proteins 0.000 description 19
- 239000000047 product Substances 0.000 description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 235000009200 high fat diet Nutrition 0.000 description 12
- 241000699670 Mus sp. Species 0.000 description 10
- 241000192142 Proteobacteria Species 0.000 description 10
- 108010058651 thioglucosidase Proteins 0.000 description 10
- 235000021590 normal diet Nutrition 0.000 description 9
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 8
- 210000004534 cecum Anatomy 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 235000006694 eating habits Nutrition 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- -1 etc.) Substances 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 241000699666 Mus <mouse, genus> Species 0.000 description 5
- 235000013361 beverage Nutrition 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 230000001575 pathological effect Effects 0.000 description 5
- 241000605716 Desulfovibrio Species 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 239000013589 supplement Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 240000007124 Brassica oleracea Species 0.000 description 3
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000009508 confectionery Nutrition 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 230000035784 germination Effects 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 108020004465 16S ribosomal RNA Proteins 0.000 description 2
- FWBHETKCLVMNFS-UHFFFAOYSA-N 4',6-Diamino-2-phenylindol Chemical compound C1=CC(C(=N)N)=CC=C1C1=CC2=CC=C(C(N)=N)C=C2N1 FWBHETKCLVMNFS-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- 206010003210 Arteriosclerosis Diseases 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
- 208000023275 Autoimmune disease Diseases 0.000 description 2
- 235000004221 Brassica oleracea var gemmifera Nutrition 0.000 description 2
- 235000012905 Brassica oleracea var viridis Nutrition 0.000 description 2
- 244000308368 Brassica oleracea var. gemmifera Species 0.000 description 2
- 244000308180 Brassica oleracea var. italica Species 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 206010015150 Erythema Diseases 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 244000088415 Raphanus sativus Species 0.000 description 2
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 244000269722 Thea sinensis Species 0.000 description 2
- 208000011775 arteriosclerosis disease Diseases 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 231100000321 erythema Toxicity 0.000 description 2
- 206010016256 fatigue Diseases 0.000 description 2
- 238000000227 grinding Methods 0.000 description 2
- 244000005709 gut microbiome Species 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 235000013772 propylene glycol Nutrition 0.000 description 2
- 238000010008 shearing Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 235000013616 tea Nutrition 0.000 description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- 229940058015 1,3-butylene glycol Drugs 0.000 description 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 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
- 206010003827 Autoimmune hepatitis Diseases 0.000 description 1
- 241000219198 Brassica Species 0.000 description 1
- 235000011331 Brassica Nutrition 0.000 description 1
- 235000011332 Brassica juncea Nutrition 0.000 description 1
- 244000178993 Brassica juncea Species 0.000 description 1
- 235000008537 Brassica juncea var. integrifolia Nutrition 0.000 description 1
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 description 1
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 description 1
- 240000007154 Coffea arabica Species 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 239000011627 DL-alpha-tocopherol Substances 0.000 description 1
- 235000001815 DL-alpha-tocopherol Nutrition 0.000 description 1
- 241001571085 Desulfovibrionales Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000032928 Dyslipidaemia Diseases 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 240000008620 Fagopyrum esculentum Species 0.000 description 1
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- 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 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
- 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
- 206010020772 Hypertension 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
- 239000002211 L-ascorbic acid Substances 0.000 description 1
- 235000000069 L-ascorbic acid Nutrition 0.000 description 1
- 238000011050 LAL assay Methods 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
- 208000017170 Lipid metabolism disease Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 244000294411 Mirabilis expansa Species 0.000 description 1
- 235000015429 Mirabilis expansa Nutrition 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 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
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 description 1
- 229960002079 calcium pantothenate Drugs 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000005018 casein Substances 0.000 description 1
- 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 1
- 235000021240 caseins Nutrition 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 235000016213 coffee Nutrition 0.000 description 1
- 235000013353 coffee beverage Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000006059 cover glass Substances 0.000 description 1
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007893 endotoxin activity Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000012632 fluorescent imaging Methods 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 125000004383 glucosinolate group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000021384 green leafy vegetables Nutrition 0.000 description 1
- 230000036433 growing body Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000008099 melanin synthesis Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 235000013536 miso Nutrition 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 235000005152 nicotinamide Nutrition 0.000 description 1
- 239000011570 nicotinamide Substances 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 235000019449 other food additives Nutrition 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 235000013555 soy sauce Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 230000007863 steatosis Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 238000000194 supercritical-fluid extraction Methods 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 244000117494 takana Species 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 238000003809 water extraction Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Images
Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Description
本発明は、リポポリサッカライド（ＬＰＳ）産生抑制剤、及びＬＰＳ産生抑制用の食品組成物に関する。 The present invention relates to a lipopolysaccharide (LPS) production inhibitor and a food composition for suppressing LPS production.
ＬＰＳは、グラム陰性細菌の細胞壁外膜の構成成分であり、内毒素（エンドトキシン）として知られている。エンドトキシンは、免疫系細胞を活性化し、炎症性サイトカインを上昇させることが知られている。炎症性サイトカインが上昇した状態が継続すると、生体は慢性炎症の状態になり、生活習慣病、動脈硬化、癌、アルツハイマー病、パーキンソン病、種々の自己免疫病、うつ病、慢性疲労などの慢性疾病の基礎病態となり得ると考えられている。 LPS is a component of the outer cell wall of Gram-negative bacteria and is known as endotoxin. Endotoxin is known to activate immune system cells and raise inflammatory cytokines. If the inflammatory cytokine level continues to rise, the body becomes chronically inflamed, and chronic diseases such as lifestyle-related diseases, arteriosclerosis, cancer, Alzheimer's disease, Parkinson's disease, various autoimmune diseases, depression, and chronic fatigue. It is thought that it can be the basic pathological condition of.
ところで、ブロッコリー等のアブラナ科植物には、グルコシノレートの一種であるグルコラファニン（ＧＲ；スルフォラファングルコシノレートとも呼ばれる）が豊富に含まれていることが知られている。
ＧＲを摂取すると、生体内のミロシナーゼによってスルフォラファン（ＳＦＮ）に代謝される。ＳＦＮは、様々な疾病に対しての効果が知られている。
ブロッコリー等のアブラナ科植物の抽出物やスルフォラファンには、皮脂産生促進作用（特許文献１）やメラニン産生抑制作用（特許文献２）があることが報告されており、皮膚疾患用の医薬品や美白用化粧料等への適用が提案されている。また、経口投与等した場合の人体への安全性も確認されている成分である。
By the way, it is known that cruciferous plants such as broccoli are rich in glucoraphanin (GR; also called sulforaphane glucosinolate), which is a kind of glucosinolate.
When GR is ingested, it is metabolized to sulforaphane (SFN) by in vivo myrosinase. SFN is known to be effective against various diseases.
It has been reported that extracts of cruciferous plants such as broccoli and sulforaphane have a sebum production promoting action (Patent Document 1) and a melanin production suppressing action (Patent Document 2), and are used for skin diseases and whitening. It has been proposed to be applied to cosmetics and the like. In addition, it is a component that has been confirmed to be safe for the human body when orally administered.
血中ＬＰＳが高値の状態が慢性化すると、慢性炎症の状態に起因する種々の疾患や病態が生じるリスクが高まり、ＬＰＳ産生を抑制することが望ましい。また、近年の消費者の健康志向の高まりから、日常の食事等で健康を管理したいという需要があり、セルフメディケーションに有用なサプリメントや機能性食品などが注目されている。
かかる状況に鑑みて、本発明は、ＬＰＳの産生を抑制し得る剤又は食品組成物を提供することを目的とする。
When the state of high blood LPS becomes chronic, the risk of developing various diseases and pathological conditions due to the state of chronic inflammation increases, and it is desirable to suppress LPS production. In addition, due to the growing health consciousness of consumers in recent years, there is a demand for managing health through daily meals and the like, and supplements and functional foods useful for self-medication are attracting attention.
In view of such circumstances, it is an object of the present invention to provide an agent or food composition capable of suppressing the production of LPS.
本発明者らは、上記課題を解決するべく鋭意研究の末、アブラナ科植物等に豊富に含まれるＧＲやその代謝物であるＳＦＮを経口摂取すると、腸内細菌叢が改善され、ＬＰＳの産生を抑制できることを見出し、本発明を完成させた。 After diligent research to solve the above problems, the present inventors orally ingested GR and its metabolite SFN, which are abundant in cruciferous plants, etc., to improve the intestinal flora and produce LPS. We have found that it is possible to suppress the above, and completed the present invention.
本発明の一態様は、ＧＲ及び／又はＳＦＮを有効成分として含有する、ＬＰＳ産生抑制剤である。
本発明の別の態様は、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上を有効成分として含有する、ＬＰＳ産生抑制剤である。ここで、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、通常、ＧＲ及び／又はＳＦＮを含有する。また、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッ
コリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物であることが好ましい。
本発明のＬＰＳ産生抑制剤において、ＧＲ及び／又はＳＦＮは、１日当たり３０ｍｇ以上で投与されるものであることが好ましい。
One aspect of the present invention is an LPS production inhibitor containing GR and / or SFN as an active ingredient.
Another aspect of the present invention is an LPS production inhibitor containing at least one selected from cruciferous plants, an extract thereof or a fraction thereof, and a pulverized product thereof as an active ingredient. Here, cruciferous plants, extracts thereof or fractions thereof, and ground products thereof usually contain GR and / or SFN. Further, the cruciferous plant, its extract or its fraction, and its crushed product are preferably broccoli sprout or broccoli seed, its extract or its fraction, and its crushed product.
In the LPS production inhibitor of the present invention, GR and / or SFN is preferably administered in an amount of 30 mg or more per day.
本発明の別の態様は、ＧＲ及び／又はＳＦＮを有効成分として含有する、ＬＰＳ産生抑制用の食品組成物である。
本発明の別の態様は、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上を有効成分として含有する、ＬＰＳ産生抑制用の食品組成物である。ここで、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、通常、ＧＲ及び／又はＳＦＮを含有する。また、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物であることが好ましい。
本発明のＬＰＳ産生抑制用の食品組成物において、ＧＲ及び／又はＳＦＮは、１日当たり３０ｍｇ以上で摂取されるものであることが好ましい。
かかる食品組成物は、好ましくは飲料又はサプリメントである。また、かかる食品組成物の好ましい態様として、機能性表示食品又は特定保健用食品が挙げられる。
Another aspect of the present invention is a food composition for suppressing LPS production, which contains GR and / or SFN as an active ingredient.
Another aspect of the present invention is a food composition for suppressing LPS production, which contains at least one selected from cruciferous plants, an extract thereof or a fraction thereof, and a pulverized product thereof as an active ingredient. Here, cruciferous plants, extracts thereof or fractions thereof, and ground products thereof usually contain GR and / or SFN. Further, the cruciferous plant, its extract or its fraction, and its crushed product are preferably broccoli sprout or broccoli seed, its extract or its fraction, and its crushed product.
In the food composition for suppressing LPS production of the present invention, GR and / or SFN is preferably ingested in an amount of 30 mg or more per day.
Such food compositions are preferably beverages or supplements. Moreover, as a preferable embodiment of such a food composition, a food with a functional claim or a food for specified health use can be mentioned.
本発明の別の態様は、ＧＲ及び／又はＳＦＮを有効成分として含有する、腸内細菌叢改善剤である。
本発明の別の態様は、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上を有効成分として含有する、腸内細菌叢改善剤である。ここで、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、後述の通り、通常、ＧＲ及び／又はＳＦＮを含有する。また、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物であることが好ましい。
本発明の腸内細菌叢改善剤において、ＧＲ及び／又はＳＦＮは、１日当たり３０ｍｇ以上で投与されるものであることが好ましい。
Another aspect of the present invention is an intestinal bacterial flora improving agent containing GR and / or SFN as an active ingredient.
Another aspect of the present invention is an intestinal bacterial flora improving agent containing at least one selected from cruciferous plants, an extract thereof or a fraction thereof, and a pulverized product thereof as an active ingredient. Here, cruciferous plants, extracts thereof or fractions thereof, and pulverized products thereof usually contain GR and / or SFN as described later. Further, the cruciferous plant, its extract or its fraction, and its crushed product are preferably broccoli sprout or broccoli seed, its extract or its fraction, and its crushed product.
In the intestinal bacterial flora improving agent of the present invention, GR and / or SFN is preferably administered in an amount of 30 mg or more per day.
本発明の別の態様は、ＧＲ及び／又はＳＦＮを有効成分として含有する、腸内細菌叢改善用の食品組成物である。
本発明の別の態様は、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上を有効成分として含有する、腸内細菌叢改善用の食品組成物である。ここで、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、後述の通り、通常、ＧＲ及び／又はＳＦＮを含有する。また、アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物であることが好ましい。
本発明の腸内細菌叢改善用の食品組成物において、ＧＲ及び／又はＳＦＮは、１日当たり３０ｍｇ以上で摂取されるものであることが好ましい。
かかる食品組成物は、好ましくは飲料又はサプリメントである。また、かかる食品組成物の好ましい態様として、機能性表示食品又は特定保健用食品が挙げられる。
Another aspect of the present invention is a food composition for improving the intestinal flora, which contains GR and / or SFN as an active ingredient.
Another aspect of the present invention is a food composition for improving the intestinal bacterial flora, which contains at least one selected from cruciferous plants, an extract thereof or a fraction thereof, and a pulverized product thereof as an active ingredient. Here, cruciferous plants, extracts thereof or fractions thereof, and pulverized products thereof usually contain GR and / or SFN as described later. Further, the cruciferous plant, its extract or its fraction, and its crushed product are preferably broccoli sprout or broccoli seed, its extract or its fraction, and its crushed product.
In the food composition for improving the intestinal bacterial flora of the present invention, GR and / or SFN is preferably ingested in an amount of 30 mg or more per day.
Such food compositions are preferably beverages or supplements. Moreover, as a preferable embodiment of such a food composition, a food with a functional claim or a food for specified health use can be mentioned.
本発明によれば、腸内細菌叢を改善し、ＬＰＳの産生を抑制するという、ＧＲ及びＳＦＮの新たな用途が提供され、これらを含有する剤又は食品組成物が提供される。本発明のＬＰＳ産生抑制剤、ＬＰＳ産生抑制用の食品組成物、腸内細菌叢改善剤、及び腸内細菌叢改善用の食品組成物は、ＬＰＳが高値であることに関連する疾患や病態の予防及び／又は改善に有用である。特に本発明の食品組成物は、機能性表示食品や特定保健用食品として消費者の健康志向にアピールするものとなり得る。 According to the present invention, new uses of GR and SFN for improving the intestinal bacterial flora and suppressing the production of LPS are provided, and agents or food compositions containing them are provided. The LPS production inhibitor, the food composition for suppressing LPS production, the intestinal bacterial flora improving agent, and the food composition for improving the intestinal bacterial flora of the present invention are used for diseases and pathological conditions related to high LPS levels. Useful for prevention and / or improvement. In particular, the food composition of the present invention can appeal to consumers' health consciousness as a food with functional claims or a food for specified health use.
本発明のＬＰＳ産生抑制剤及びＬＰＳ産生抑制用の食品組成物は、有効成分として、グルコラファニン（ＧＲ）及び／又はスルフォラファン（ＳＦＮ）を含有する。
ＧＲはＳＦＮの前駆体であり、ＧＲのミロシナーゼによる代謝物がＳＦＮであり、ＳＦＮが活性本体であると考えられている。
The LPS production inhibitor and the food composition for suppressing LPS production of the present invention contain glucoraphanin (GR) and / or sulforaphane (SFN) as active ingredients.
GR is a precursor of SFN, the metabolite of GR by myrosinase is SFN, and SFN is considered to be the active body.
ＧＲはアブラナ科植物に多く含有されていることが知られており、本発明においてＧＲは、精製された状態で剤や食品組成物に含有されてもよいし、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上の状態で含有されてもよい。 It is known that GR is abundantly contained in cruciferous plants, and in the present invention, GR may be contained in an agent or food composition in a purified state, or is a cruciferous plant, an extract thereof, or It may be contained in one or more states selected from the fraction and the ground product thereof.
ＳＦＮはＧＲがミロシナーゼによって代謝されることで生成される。
アブラナ科植物は、内在的にミロシナーゼを保有している。植物体が破砕、摩砕、粉砕、せん断、搾汁等の工程によって破壊されると、内在するミロシナーゼがＧＲと反応し、ＧＲはＳＦＮに代謝される。植物体を破砕等の工程によって破壊する前に加熱処理を行い、ミロシナーゼを失活させると、ＧＲからＳＦＮの代謝は行われない。すなわち、アブラナ科植物の抽出物もしくはその分画、又はアブラナ科植物の粉砕物は、通常ＧＲ及び／又はＳＦＮを含有する。
SFN is produced by the metabolism of GR by myrosinase.
Cruciferous plants have an endogenous myrosinase. When a plant is destroyed by processes such as crushing, grinding, crushing, shearing, and squeezing, the internal myrosinase reacts with GR, and GR is metabolized to SFN. If heat treatment is performed to inactivate myrosinase before the plant is destroyed by a process such as crushing, the metabolism of SFN from GR is not performed. That is, the cruciferous plant extract or its fraction, or the cruciferous plant pulverized product, usually contains GR and / or SFN.
本発明においてＳＦＮは、精製された状態で剤や食品組成物に含有されてもよいし、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上の状態で含有されてもよい。
なお、ＧＲを摂取すると生体内でミロシナーゼによる代謝を受けてＳＦＮになるため、ＧＲを含有するアブラナ科植物の状態を含有する本発明の剤や食品組成物を投与又は摂取した場合は、生体内でＧＲが代謝されてその代謝産物であるＳＦＮが活性を発揮すると考えられる。
In the present invention, SFN may be contained in an agent or food composition in a purified state, or may be contained in one or more states selected from cruciferous plants, extracts thereof or fractions thereof, and pulverized products thereof. May be done.
When GR is ingested, it is metabolized by myrosinase in vivo to become SFN. Therefore, when the agent or food composition of the present invention containing the state of a cruciferous plant containing GR is administered or ingested, it is in vivo. It is considered that GR is metabolized and SFN, which is a metabolite thereof, exerts its activity.
前記アブラナ科植物としては、特に限定されないが、例えば、ブロッコリー、ケール、キャベツ、カリフラワー、高菜、アブラナ、カラシナ、大根、大根葉、野沢菜、小松菜、白菜、芽キャベツ、プチヴェール（ケールと芽キャベツの交配品）等が挙げられる。
また、植物の部分としては、植物の成長体（芽、葉、茎、根、又は花など）でも、スプラウト（発芽体）でも、種子でもよく、特に制限されない。
これらのうちより好ましいのは、アブラナ科アブラナ属（Brassica）に属するブロッコリー（Brassica oleracea var. italica）である。さらに、ＧＲ及び／又はＳＦＮの含有量の高さから、ブロッコリーのスプラウト又は種子が特に好ましい。
The cruciferous plants are not particularly limited, but for example, broccoli, kale, cabbage, cauliflower, takana, abrana, mustard greens, radish, radish leaves, nozawa greens, komatsuna, white vegetables, Brussels sprouts, and petit veil (crossing of kale and Brussels sprouts). Goods) and the like.
The part of the plant may be a growing body of the plant (bud, leaf, stem, root, flower, etc.), a sprout (sprouting body), or a seed, and is not particularly limited.
More preferred of these are broccoli (Brassica oleracea var. Italica) belonging to the Brassicaceae genus Brassica. In addition, broccoli sprouts or seeds are particularly preferred due to their high GR and / or SFN content.
ブロッコリースプラウトからＧＲ及び／又はＳＦＮを抽出する場合は、その含有量が減少傾向になる成長体になる前であれば発芽後何日後であってもよいが、好ましくは発芽後
１〜１０日後、より好ましくは１〜３日後のスプラウトを用いる。また、ＧＲ及び／又はＳＦＮの含有量が、好ましくは５０〜３５０ｍｇ／１００ｇ（湿重量）、より好ましくは１５０〜３３０ｍｇ／１００ｇ（湿重量）、さらに好ましくは２５０〜３００ｍｇ／１００ｇ（湿重量）のブロッコリースプラウトを用いることが好ましい。
When GR and / or SFN is extracted from broccoli sprout, it may be several days after germination as long as it is before the growth body whose content tends to decrease, but preferably 1 to 10 days after germination. More preferably, sprout after 1 to 3 days is used. The GR and / or SFN content is preferably 50 to 350 mg / 100 g (wet weight), more preferably 150 to 330 mg / 100 g (wet weight), and even more preferably 250 to 300 mg / 100 g (wet weight). It is preferable to use broccoli sprout.
ブロッコリースプラウト等を含むアブラナ科植物からのＧＲ及び／又はＳＦＮの取得は、周知の方法により行うことができる。
例えば、ＧＲは、植物の一部または全体をそのまま又は乾燥粉砕したものを溶媒等で抽出して取得することができ、溶媒としては、水、低級１価アルコール（メタノール、エタノール、１−プロパノール、２−プロパノール、１−ブタノール、２−ブタノール等）、液状多価アルコール（グリセリン、プロピレングリコール、１，３−ブチレングリコール等）、低級エステル（酢酸エチル等）、炭化水素（ベンゼン、ヘキサン、ペンタン等）、ケトン類（アセトン、メチルエチルケトン等）、エーテル類（ジエチルエーテル、テトラヒドロフラン、ジプロピルエーテル等）、アセトニトリル等が挙げられ、それらの一種又は２種以上を用いることができる。本発明の剤又は食品組成物は経口で投与又は摂取されることを考慮すると、抽出溶媒としては、水、エタノール、又は含水エタノールが特に好ましい。好ましい抽出方法の例としては、例えば熱水（９０〜１００℃）で、１０〜３０分間抽出する方法や、０〜１００体積％の含水エタノールで室温又は加温して１〜１０日間抽出する方法が挙げられ、その抽出液をさらに分画・精製してもよい。その他に、超臨界抽出によってＧＲを抽出してもよい。
Acquisition of GR and / or SFN from cruciferous plants including broccoli sprout and the like can be carried out by a well-known method.
For example, GR can be obtained by extracting a part or the whole of a plant as it is or pulverized by drying with a solvent or the like, and the solvent includes water, lower monohydric alcohol (methanol, ethanol, 1-propanol, etc.). 2-Propanol, 1-butanol, 2-butanol, etc.), liquid polyhydric alcohols (glycerin, propylene glycol, 1,3-butylene glycol, etc.), lower esters (ethyl acetate, etc.), hydrocarbons (benzene, hexane, pentane, etc.) ), Ketones (acetone, methyl ethyl ketone, etc.), ethers (diethyl ether, tetrahydrofuran, dipropyl ether, etc.), acetonitrile and the like, and one or more of them can be used. Considering that the agent or food composition of the present invention is orally administered or ingested, water, ethanol, or hydrous ethanol is particularly preferable as the extraction solvent. Examples of preferable extraction methods include, for example, a method of extracting with hot water (90 to 100 ° C.) for 10 to 30 minutes, and a method of extracting at room temperature or heating with 0 to 100% by volume of hydrous ethanol for 1 to 10 days. The extract may be further fractionated and purified. Alternatively, GR may be extracted by supercritical extraction.
ＧＲからＳＦＮを得る方法としては、ＧＲとミロシナーゼを反応させればよく、その方法は限定されない。例えば、ＧＲを含むアブラナ科植物を、加熱せずに破砕、摩砕、粉砕、せん断、搾汁等することでＧＲと内在のミロシナーゼを反応させ、ＳＦＮに代謝させる方法や、ＧＲにミロシナーゼを添加してＳＦＮに代謝させる方法等が挙げられる。ＳＦＮは、これらの方法にてＧＲから代謝されたＳＦＮを含む原料から、ＧＲと同様の方法（例えば、前段落に記載の抽出等の方法）にて取得することができる。 As a method for obtaining SFN from GR, GR may be reacted with myrosinase, and the method is not limited. For example, a method of reacting GR with intrinsic myrosinase by crushing, grinding, crushing, shearing, squeezing, etc., a cruciferous plant containing GR without heating and metabolizing it to SFN, or adding myrosinase to GR. Then, a method of metabolizing to SFN and the like can be mentioned. SFN can be obtained from a raw material containing SFN metabolized from GR by these methods by the same method as GR (for example, the method such as extraction described in the previous paragraph).
剤、食品組成物、又は抽出物等の中のＧＲの濃度測定は、当業者周知の方法により行うことができる。例えば、高速液体クロマトグラフィー（ＨＰＬＣ）法を用いることができ、具体的な方法としては、Faheyらの方法（Fahey et al., Proc. Natl. Acad. Sci. USA,
94, 10367-10372, 1997）等に従って行うことができる。
剤、食品組成物、又は抽出物等の中のＳＦＮの濃度測定は、当業者周知の方法により行うことができる。例えば、高速液体クロマトグラフィー（ＨＰＬＣ）法を用いることができ、具体的な方法としては、Hanらの方法（Han et al., Int. J. Mol. Sci., 12, 1854-1861, 2011）等に従って行うことができる。
The concentration of GR in an agent, food composition, extract or the like can be measured by a method well known to those skilled in the art. For example, a high performance liquid chromatography (HPLC) method can be used, and as a specific method, the method of Fahey et al., Proc. Natl. Acad. Sci. USA,
It can be done according to 94, 10367-10372, 1997) and so on.
The concentration of SFN in an agent, food composition, extract or the like can be measured by a method well known to those skilled in the art. For example, a high performance liquid chromatography (HPLC) method can be used, and specific methods include the method of Han et al. (Han et al., Int. J. Mol. Sci., 12, 1854-1861, 2011). Etc. can be performed.
本発明のＬＰＳ産生抑制剤の投与形態としては、例えば、錠剤、被覆錠剤、カプセル剤、顆粒剤、散剤、溶液、シロップ剤、乳液等による経口投与を好ましく挙げることができる。なお、非経口投与形態が排除されるわけではなく、局所組織投与や、注射による皮下、皮内、筋肉内、静脈内投与等によってもよい。
本発明のＬＰＳ産生抑制剤は、賦形剤、結合剤、崩壊剤、滑沢剤、着色剤、矯味矯臭剤、溶解補助剤、懸濁剤、コーティング剤などの医薬等の製剤技術分野において通常使用し得る既知の補助剤を用いて製剤化することができる。
また、本発明のＬＰＳ産生抑制剤の分類としては、医薬品または医薬部外品の態様であってもよい。
As the administration form of the LPS production inhibitor of the present invention, for example, oral administration with tablets, coated tablets, capsules, granules, powders, solutions, syrups, emulsions and the like can be preferably mentioned. The parenteral administration form is not excluded, and may be administered by local tissue administration, subcutaneous administration by injection, intradermal administration, intramuscular administration, intravenous administration, or the like.
The LPS production inhibitor of the present invention is usually used in the field of pharmaceuticals such as excipients, binders, disintegrants, lubricants, colorants, flavoring agents, solubilizing agents, suspending agents, coating agents and the like. It can be formulated with known adjuvants that can be used.
Further, the classification of the LPS production inhibitor of the present invention may be in the form of a drug or a quasi-drug.
本発明のＬＰＳ産生抑制用の食品組成物としては、例えば、飲料（ジュース、コーヒー、紅茶、茶、炭酸飲料、スポーツ飲料等）、菓子類（ガム、キャンディー、キャラメル、チョコレート、クッキー、スナック、ゼリー、グミ、錠菓等）、麺類（そば、うどん、ラ
ーメン等）、乳製品（ミルク、アイスクリーム、ヨーグルト等）、調味料（味噌、醤油等）、スープ類、をはじめとする一般食品や、健康食品（錠剤、カプセル等）、栄養補助食品（サプリメント、栄養ドリンク等）が挙げられる。
これら食品組成物には、その種類に応じて種々の成分を配合することができ、例えば、ブドウ糖、果糖、ショ糖、マルトース、ソルビトール、ステビオサイド、コーンシロップ、乳糖、クエン酸、酒石酸、リンゴ酸、コハク酸、乳酸、Ｌ−アスコルビン酸、ｄｌ−α−トコフェロール、エリソルビン酸ナトリウム、グリセリン、プロピレングリコール、グリセリン脂肪酸エステル、ポリグリセリン脂肪酸エステル、ショ糖脂肪酸エステル、ソルビタン脂肪酸エステル、プロピレングリコール脂肪酸エステル、アラビアガム、カラギーナン、カゼイン、ゼラチン、ペクチン、寒天、ビタミンＢ類、ニコチン酸アミド、パントテン酸カルシウム、アミノ酸類、カルシウム塩類、色素、香料、保存剤等の食品添加物を任意に使用することができる。
Examples of the food composition for suppressing LPS production of the present invention include beverages (juice, coffee, tea, tea, carbonated beverages, sports beverages, etc.) and confectionery (gum, candy, caramel, chocolate, cookies, snacks, jelly). , Gummy, candy, etc.), noodles (soba, udon, ramen, etc.), dairy products (milk, ice cream, yogurt, etc.), seasonings (miso, soy sauce, etc.), soups, and other general foods Examples include health foods (tablets, capsules, etc.) and nutritional supplements (supplements, nutritional drinks, etc.).
Various ingredients can be blended in these food compositions depending on the type, for example, glucose, fructose, sucrose, maltose, sorbitol, stebioside, corn syrup, lactose, citric acid, tartrate, malic acid, etc. Succinic acid, lactic acid, L-ascorbic acid, dl-α-tocopherol, sodium erythorbicate, glycerin, propylene glycol, glycerin fatty acid ester, polyglycerin fatty acid ester, sucrose fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, Arabic gum , Carrageenan, casein, gelatin, pectin, agar, vitamin Bs, nicotinic acid amide, calcium pantothenate, amino acids, calcium salts, pigments, fragrances, preservatives and other food additives can be optionally used.
本発明のＬＰＳ産生抑制剤は、特に限定されないが、ＧＲ及び／又はＳＦＮを合計で０．０３質量％以上含有していることが好ましく、１質量％以上含有していることがより好ましく、５質量％以上含有していることが特に好ましい。
また、本発明のＬＰＳ産生抑制用の食品組成物は、特に限定されないが、ＧＲ及び／又はＳＦＮを合計で０．０１質量％以上含有していることが好ましく、０．０５質量％以上含有していることがより好ましく、０．２５質量％以上含有していることが特に好ましい。
The LPS production inhibitor of the present invention is not particularly limited, but preferably contains GR and / or SFN in a total amount of 0.03% by mass or more, and more preferably 1% by mass or more. It is particularly preferable that the content is mass% or more.
The food composition for suppressing LPS production of the present invention is not particularly limited, but preferably contains GR and / or SFN in a total amount of 0.01% by mass or more, and preferably 0.05% by mass or more. It is more preferable that the content is 0.25% by mass or more, and it is particularly preferable that the content is 0.25% by mass or more.
本発明のＬＰＳ産生抑制剤の投与量、又はＬＰＳ産生抑制用の食品組成物の摂取量は、投与／摂取する対象がヒトである場合、その性別、症状、年齢、投与方法によって異なるが、ＧＲ及び／又はＳＦＮが通常、成人（体重６０ｋｇ程度）１日当たり３０ｍｇ以上であることが、ＬＰＳ産生抑制作用が十分に発揮される観点から好ましい。この１日当たりの量を一度に又は数回に分けて投与／摂取することができ、そのタイミングとしては、食前、食後、食間のいずれでもよい。また、投与／摂取期間は特に限定されない。
なお、「１日当たり３０ｍｇ以上」とは、食品組成物の形態によって異なるが、表示される１日の摂取目安量や、通常１度で消費する飲みきりタイプの飲料であれば１本当たりに含まれる量を指すものである。
The dose of the LPS production inhibitor of the present invention or the intake of the food composition for suppressing LPS production varies depending on the sex, symptom, age, and administration method of a human being to be administered / ingested, but GR And / or SFN is usually 30 mg or more per day for an adult (body weight of about 60 kg), which is preferable from the viewpoint of sufficiently exerting the LPS production inhibitory effect. This daily amount can be administered / ingested at one time or in several divided doses, and the timing may be any of pre-meal, post-meal, and inter-meal. The administration / intake period is not particularly limited.
In addition, "30 mg or more per day" varies depending on the form of the food composition, but it is included in the displayed daily intake guideline amount and in the case of a single-drink type beverage that is normally consumed at one time. It refers to the amount of food that is consumed.
本明細書において「ＬＰＳ産生抑制」作用とは、血中、特に血漿中のＬＰＳ濃度を低下させる作用、又は、血中、特に血漿中のＬＰＳ濃度の上昇を抑制する作用をいう。すなわち、本発明のＬＰＳ産生抑制剤及びＬＰＳ産生抑制用の食品組成物は、血中のＬＰＳ濃度が高めの人や血中のＬＰＳ濃度が気になる人の食生活の改善に役立つ機能性を有するものである。
また、本明細書において「ＬＰＳ産生抑制」作用とは、血中、特に血漿中のＬＰＳ結合タンパク質（ＬＢＰ）濃度を低下させる作用、又は、血中、特に血漿中のＬＢＰ濃度の上昇を抑制する作用であってもよい。これは、後述の実施例で示されるように、血中、特に血漿中のＬＰＳ濃度は、血漿中のＬＢＰ濃度とパラレルな関係にあり、ともにＧＲ投与により抑制されることに基づく。本発明における「ＬＰＳ産生抑制」作用は、ＬＢＰ濃度を測定してその低下又は上昇抑制を観察することにより評価することができる。したがって、本発明のＬＰＳ産生抑制剤及びＬＰＳ産生抑制用の食品組成物は、血中のＬＢＰ濃度が高めの人や血中のＬＢＰ濃度が気になる人の食生活の改善に役立つ機能性を有するものでもある。
As used herein, the "LPS production inhibitory" action refers to an action of lowering the LPS concentration in blood, particularly plasma, or an action of suppressing an increase in LPS concentration in blood, particularly plasma. That is, the LPS production inhibitor and the food composition for suppressing LPS production of the present invention have functionality that is useful for improving the eating habits of a person having a high LPS concentration in blood or a person who is concerned about the LPS concentration in blood. Have.
Further, in the present specification, the "LPS production inhibitory" action is an action of lowering the LPS-binding protein (LBP) concentration in blood, particularly in plasma, or an action of suppressing an increase in LBP concentration in blood, particularly plasma. It may be an action. This is based on the fact that the LPS concentration in blood, especially in plasma, has a parallel relationship with the LBP concentration in plasma, and both are suppressed by GR administration, as shown in Examples described later. The "LPS production inhibitory" effect in the present invention can be evaluated by measuring the LBP concentration and observing its decrease or increase. Therefore, the LPS production inhibitor and the food composition for suppressing LPS production of the present invention have functionality that is useful for improving the eating habits of a person having a high blood LBP concentration or a person who is concerned about the blood LBP concentration. It also has.
後述の実施例にて示される通り、本発明のＬＰＳ産生抑制剤の作用は、ＧＲ及び／ＳＦＮによって腸内細菌叢が改善されることにより発揮されるものであると考えられる。ここで、「腸内細菌叢の改善」とは、腸内細菌叢内のＬＰＳ産生菌（通常はエンドトキシン活性を有するＬＰＳを産生する、プロテオバクテリア門に属するグラム陰性菌を指す）の存
在数の割合もしくは絶対数が減少する、又は増加が抑制されることをいう。また、さらに詳しく述べれば、「腸内細菌叢の改善」とは、腸内細菌叢内のＬＰＳ産生菌の中でもプロテオバクテリア門に属するデスルフォビブリオ科に属する菌の存在数の割合もしくは絶対数が減少する、又は増加が抑制されることをいう。
したがって、本発明の他の態様として、ＧＲ及び／又はＳＦＮを有効成分として含有する、腸内細菌叢改善剤も提供される。
本発明の腸内細菌叢改善剤は、食品組成物に含有させる態様とすることも好ましい。すなわち、本発明のさらなる側面として、ＧＲ及び／又はＳＦＮを有効成分として含有する、腸内細菌叢改善用の食品組成物が提供される。
本発明の腸内細菌叢改善剤及び腸内細菌叢改善用の食品組成物の有効成分、投与量、態様等の具体的な説明については、前述したＬＰＳ産生抑制剤及びＬＰＳ産生抑制用の食品組成物の説明に準ずる。
As shown in Examples described later, it is considered that the action of the LPS production inhibitor of the present invention is exerted by improving the intestinal bacterial flora by GR and / SFN. Here, "improvement of the intestinal flora" refers to the number of LPS-producing bacteria (which usually refers to Gram-negative bacteria belonging to the phylum Proteobacteria that produce LPS having endotoxin activity) in the intestinal flora. It means that the ratio or absolute number decreases or the increase is suppressed. More specifically, "improvement of the intestinal flora" means the ratio or absolute number of LPS-producing bacteria in the intestinal flora that belong to the family Desulfovibrionales belonging to the phylum Proteobacteria. It means that the decrease or increase is suppressed.
Therefore, as another aspect of the present invention, an intestinal bacterial flora improving agent containing GR and / or SFN as an active ingredient is also provided.
It is also preferable that the intestinal bacterial flora improving agent of the present invention is contained in a food composition. That is, as a further aspect of the present invention, there is provided a food composition for improving the intestinal bacterial flora, which contains GR and / or SFN as an active ingredient.
For specific explanations of the active ingredient, dose, mode, etc. of the intestinal bacterial flora improving agent and the food composition for improving the intestinal bacterial flora of the present invention, the above-mentioned LPS production inhibitor and food for suppressing LPS production are described. Follow the description of the composition.
本発明のＬＰＳ産生抑制用の食品組成物及び腸内細菌叢改善用の食品組成物は、前述した機能性や生体に対する有用な作用に基づいて、好適に機能性表示食品や特定保健用食品とすることができる。 The food composition for suppressing LPS production and the food composition for improving the intestinal bacterial flora of the present invention are suitably combined with foods with functional claims and foods for specified health use based on the above-mentioned functionality and useful action on the living body. can do.
本発明のＬＰＳ産生抑制剤、ＬＰＳ産生抑制用の食品組成物、腸内細菌叢改善剤、及び腸内細菌叢改善用の食品組成物は、ＬＰＳが高値であることに関連する疾患や病態の予防及び／又は改善に有用となり得る。例えば、生活習慣病（肥満症、２型糖尿病、脂質異常症、高血圧、脂肪肝炎、脳卒中、心臓病）、動脈硬化、癌、アルツハイマー病、パーキンソン病、種々の自己免疫病（関節リウマチ、乾癬、自己免疫性肝炎、自己免疫性甲状腺炎、自己免疫性溶血性貧血、自己免疫性腎炎、潰瘍性大腸炎、紅班性狼瘡、シェーグレン症候群など）、うつ病、慢性疲労などの慢性疾病、等の予防及び／又は改善に効果が期待される。 The LPS production inhibitor, the food composition for suppressing LPS production, the intestinal bacterial flora improving agent, and the food composition for improving the intestinal bacterial flora of the present invention are used for diseases and pathological conditions related to high LPS levels. Can be useful for prevention and / or improvement. For example, lifestyle diseases (obesity, type 2 diabetes, dyslipidemia, hypertension, steatosis, stroke, heart disease), arteriosclerosis, cancer, Alzheimer's disease, Parkinson's disease, various autoimmune diseases (rheumatoid arthritis, psoriasis, etc.) Autoimmune hepatitis, autoimmune thyroiditis, autoimmune hemolytic anemia, autoimmune nephritis, ulcerative colitis, erythema erythema, Schegren's syndrome, etc.), depression, chronic diseases such as chronic fatigue, etc. Expected to be effective in prevention and / or improvement.
本発明に係る剤又は食品組成物の有する有用性や機能性に関しては、製品化の際に次のような表示を付してもよい。例えば、「血中ＬＰＳ濃度を低下させる機能性」、「血中ＬＰＳ濃度の上昇を抑制する機能性」、「血中ＬＰＳ濃度が高めの人の食生活の改善に役立つ機能性」、「血中ＬＰＳ濃度が気になる人の食生活の改善に役立つ機能性」、「血中ＬＰＳ濃度の上昇が気になる人の食生活の改善に役立つ機能性」、「血中ＬＢＰ濃度を低下させる機能性」、「血中ＬＢＰ濃度の上昇を抑制する機能性」、「血中ＬＢＰ濃度が高めの人の食生活の改善に役立つ機能性」、「血中ＬＢＰ濃度が気になる人の食生活の改善に役立つ機能性」、「血中ＬＢＰ濃度の上昇が気になる人の食生活の改善に役立つ機能性」、「腸内細菌叢を改善させる機能性」、「腸内のＬＰＳ産生菌を減少させる機能性」、「腸内のＬＰＳ産生菌の増加を抑制する機能性」、「腸内細菌叢の改善に役立つ機能性」等の表示が挙げられる。
なお、これらの表示は、公知の方法で容器包装手段に付すことができる。
Regarding the usefulness and functionality of the agent or food composition according to the present invention, the following labeling may be attached at the time of commercialization. For example, "functionality that lowers blood LPS concentration", "functionality that suppresses increase in blood LPS concentration", "functionality that helps improve the eating habits of people with high blood LPS concentration", "blood""Functionality that helps improve the eating habits of people who are concerned about medium LPS concentration", "Functionality that helps improve eating habits of people who are concerned about increased blood LPS concentration", "Reduces blood LBP concentration""Functionality","Functionality that suppresses the increase in blood LBP concentration", "Functionality that helps improve the eating habits of people with high blood LBP concentration", "Food of people who are concerned about blood LBP concentration""Functionality that helps improve life", "Functionality that helps improve the eating habits of people who are concerned about an increase in blood LBP concentration", "Functionality that improves the intestinal flora", "LPS production in the intestine" Labels such as "functionality to reduce bacteria", "functionality to suppress the increase of LPS-producing bacteria in the intestine", and "functionality to help improve the intestinal flora" can be mentioned.
In addition, these indications can be attached to the container packaging means by a known method.
次に実施例を挙げて本発明を詳細に説明するが、本発明はこれらの実施例に限定されるものではない。 Next, the present invention will be described in detail with reference to Examples, but the present invention is not limited to these Examples.
＜ブロッコリースプラウト抽出物の調製＞
以下の手順でＧＲを高含有するブロッコリースプラウト（ＢＳ）抽出物を調製した。
ブロッコリーの種子（Caudill Seed Co., Inc.）を発芽させ、発芽後１日間栽培して「１ｄａｙ ＢＳ」を得た。これを熱水抽出（９５℃、３０分間）に供し、ＢＳ残渣を除去
した。当該抽出液をロータリーエバポレーターを用いて約１０倍濃縮した後、デキストリンと混合し、スプレードライ法により粉末化した。最終的に得られたＢＳ抽出粉末中のＧＲ含量を高速液体クロマトグラフィー（ＨＰＬＣ）法により測定したところ、１３５ｍｇ
／ｇであった。このＢＳ抽出粉末を、後述の動物試験に使用した。
<Preparation of broccoli sprout extract>
A broccoli sprout (BS) extract having a high GR content was prepared by the following procedure.
Broccoli seeds (Caudill Seed Co., Inc.) were germinated and cultivated for 1 day after germination to obtain "1day BS". This was subjected to hot water extraction (95 ° C., 30 minutes) to remove BS residue. The extract was concentrated about 10 times using a rotary evaporator, mixed with dextrin, and pulverized by a spray-drying method. The GR content in the finally obtained BS extract powder was measured by high performance liquid chromatography (HPLC) method and found to be 135 mg.
It was / g. This BS extract powder was used in the animal test described later.
＜動物試験＞
動物試験は、「standards set forth in the Guidelines for the Care and Use of Laboratory Animals at Kanazawa University」に則って実施した。
雄性C57BL/6Jslcマウス（７週齢、日本ＳＬＣ）を用い、明暗１２時間周期の飼育室に
て試験を行った。１週間の馴化後、マウスを４群に分け（各群ｎ＝９）、各群の飼料を通常食（10% kcal from fat, D12450B, Research Diets）、０．３質量％のＧＲを含有する通常食、高脂肪食（60% kcal from fat, D12492, Research Diets）、又は０．３質量％
のＧＲを含有する高脂肪食に切り換えて１４週間摂取させた。なお、ＧＲ含有通常食及びＧＲ含有高脂肪食の飼料には、ＧＲ含量が０．３質量％となるように２．２質量％のＢＳ抽出粉末を混合した。一方、通常食及び高脂肪食の飼料にはそれぞれ、２．２質量％のデキストリンを混合した。各食餌群とも１４週間の摂取期間の後、マウスを頸椎脱臼により安楽死させ、血液及び盲腸内容物を採取した。採取した血液は、血漿調製用の採血管に入れた後、遠心分離を行い、その上清を血漿試料とした。
<Animal test>
Animal studies were conducted in accordance with "standards set forth in the Guidelines for the Care and Use of Laboratory Animals at Kanazawa University".
Using male C57BL / 6Jslc mice (7 weeks old, Japan SLC), the test was conducted in a breeding room with a 12-hour cycle of light and dark. After 1 week of acclimatization, the mice were divided into 4 groups (n = 9 in each group), and the diet of each group contained a normal diet (10% kcal from fat, D12450B, Research Diets) and 0.3% by mass GR. Normal diet, high fat diet (60% kcal from fat, D12492, Research Diets), or 0.3% by mass
The diet was switched to a high-fat diet containing GR and was ingested for 14 weeks. The feeds of the GR-containing normal diet and the GR-containing high-fat diet were mixed with 2.2% by mass of BS extract powder so that the GR content was 0.3% by mass. On the other hand, 2.2% by mass of dextrin was mixed with the normal diet and the high-fat diet, respectively. After a 14-week ingestion period in each diet group, mice were euthanized by cervical dislocation and blood and cecal contents were collected. The collected blood was placed in a blood collection tube for plasma preparation and then centrifuged, and the supernatant was used as a plasma sample.
＜血中指標の測定＞
前記血漿試料に対して、Limulus amebocyte lysate assay kit（QCL-1000; Lonza）を
用いて血漿ＬＰＳ濃度を測定した。また、前記血漿試料に対して、LBP, soluble (mouse)
ELISA kit（Enzo Life Sciences）を用いて血漿ＬＢＰ濃度を測定した。
<Measurement of blood index>
The plasma LPS concentration of the plasma sample was measured using a Limulus amebocyte lysate assay kit (QCL-1000; Lonza). In addition, for the plasma sample, LBP, soluble (mouse)
Plasma LBP concentration was measured using an ELISA kit (Enzo Life Sciences).
＜腸内細菌叢解析＞
採取した盲腸内容物からQIAamp DNA Stool Mini Kit（QIAGEN）を用いて、盲腸内細菌
由来のＤＮＡを抽出した。その後、既に報告されているKimらの方法（Kim et al., DNA RESEARCH, 20, 241-253, 2013）に従い、次世代シーケンサーGS Junior（Roche）を用いて16s rRNAの塩基配列を取得した。続いて、得られた16s rRNA塩基配列のうち、4,000リー
ド／サンプルを盲腸内細菌叢の解析に供した。前述のKimらと同様に構築したパイプライ
ン及びデータベースを使用し、ＯＴＵ（Operational Taxonomic Unit）の作成及びＢＬＡＳＴ検索による菌種帰属の同定を実施した。また、キメラ配列の排除についても前述のKimらの手法を用いて行った。
<Gut microbiota analysis>
DNA derived from cecal bacteria was extracted from the collected cecal contents using the QIAamp DNA Stool Mini Kit (QIAGEN). Then, according to the previously reported method of Kim et al. (Kim et al., DNA RESEARCH, 20, 241-253, 2013), the base sequence of 16s rRNA was obtained using the next-generation sequencer GS Junior (Roche). Subsequently, 4,000 reads / sample of the obtained 16s rRNA base sequence were subjected to analysis of the cecal bacterial flora. Using the pipeline and database constructed in the same manner as Kim et al., OTU (Operational Taxonomic Unit) was created and bacterial species attribution was identified by BLAST search. The chimeric sequence was also eliminated using the method of Kim et al. described above.
＜総菌数の測定＞
マウスから採取した盲腸内容物を滅菌したｐＨ７．４のリン酸緩衝生理食塩水（ＰＢＳ）に懸濁し、ポリトロンミキサーを用いたホモジナイズ（10,000 rpm, 1 min）を行った
後、懸濁液を100 μm孔径のセルストレーナー（ＢＤファルコン）で濾過した。濾液を遠
心分離（3,000×g, 10 min, 4℃）に供し、上清を除去した。沈殿物（細菌ペレット）に4% (w/v) パラフォルムアルデヒドを添加し、30分間静置することにより細菌を固定した。遠心分離（3,000×g, 10 min, 4℃）により上清を除いた後、固定した細菌をＰＢＳに懸
濁し、適宜希釈した後、0.2 μm孔径のメンブレンフィルター（Millipore）で濾過することで、細菌をフィルター上に捕集した。1 μg/mLのＤＡＰＩ（4',6-diamidino-2-phenylindole, Sigma）水溶液1 mLにフィルターを浸し、暗所、室温で５分間静置して染色した。染色後、無蛍光イマージョンオイル（ニコン）を１滴載せたＡＰＳコート付スライドグラス（松浪硝子）上にフィルターを置いた。続いてフィルター上に無蛍光イマージョンオイルを１滴滴下し、カバーグラスで封入した。その後、蛍光顕微鏡BIOREVO BZ-9000（キー
エンス）を用いて紫外線励起光下で１０視野の観察を行ない、青色発光した細菌数を計数して平均値を算出した。以下の式に従って、細菌液1 mL中及び盲腸内容物1 g中の総菌数
を求めた。
Ｎ1［／ｍＬ］＝（ｎ×Ｓ[μｍ2]）／（Ａ[μｍ2]×Ｖ1[ｍＬ])
（Ｎ1：細菌液1 mL中の総菌数、ｎ：１視野当たりの平均細菌数、Ｓ：フィルターの有
効濾過面積、Ａ：観察視野面積、Ｖ1：濾過した細菌液量）
<Measurement of total bacterial count>
The cecal contents collected from mice were suspended in sterile phosphate buffered saline (PBS) at pH 7.4, homogenized using a polytron mixer (10,000 rpm, 1 min), and then the suspension was 100. It was filtered with a cell strainer (BD Falcon) having a μm pore size. The filtrate was centrifuged (3,000 × g, 10 min, 4 ° C.) and the supernatant was removed. Bacteria were fixed by adding 4% (w / v) paraformaldehyde to the precipitate (bacterial pellet) and allowing it to stand for 30 minutes. After removing the supernatant by centrifugation (3,000 x g, 10 min, 4 ° C), the fixed bacteria are suspended in PBS, diluted appropriately, and then filtered through a membrane filter (Millipore) with a pore size of 0.2 μm. Bacteria were collected on the filter. The filter was immersed in 1 mL of a 1 μg / mL DAPI (4', 6-diamidino-2-phenylindole, Sigma) aqueous solution, and allowed to stand in a dark place at room temperature for 5 minutes for staining. After dyeing, the filter was placed on a slide glass (Matsunami Glass) with an APS coat on which a drop of non-fluorescent immersion oil (Nikon) was placed. Subsequently, a drop of non-fluorescent imaging oil was dropped onto the filter and sealed with a cover glass. Then, 10 fields of view were observed under ultraviolet excitation light using a fluorescence microscope BIOREVO BZ-9000 (Keyence), and the number of bacteria that emitted blue light was counted to calculate the average value. The total number of bacteria in 1 mL of bacterial solution and 1 g of cecal contents was determined according to the following formula.
N 1 [/ mL] = (n × S [μm 2 ]) / (A [μm 2 ] × V 1 [mL])
(N 1 : Total number of bacteria in 1 mL of bacterial solution, n: Average number of bacteria per field of view, S: Effective filtration area of filter, A: Observation field area, V 1 : Volume of filtered bacterial solution)
＜結果＞
各食餌群のマウスの血漿ＬＰＳ濃度を図１に示す。高脂肪食群において、ＧＲを含有する食餌を摂取した場合は、ＧＲを含有しない場合に比べて有意に血漿ＬＰＳ濃度が低値であった。この結果より、ＧＲによるＬＰＳ産生抑制効果は、ＬＰＳが高値となり得る状態においてより得られやすいことが分かる。
各食餌群のマウスの血漿ＬＢＰ濃度を図２に示す。高脂肪食群において、ＧＲを含有する食餌を摂取した場合は、ＧＲを含有しない場合に比べて有意に血漿ＬＢＰ濃度が低値であった。この結果より、ＧＲによるＬＢＰ抑制効果は、ＬＢＰが高値となり得る状態においてより得られやすいことが分かる。また、この結果は、前述の血漿ＬＰＳ濃度の結果とよく一致した。
腸内細菌叢解析による各食餌群のマウスの盲腸内細菌を門レベルで測定し、その相対菌数（割合）を図３に、盲腸内細菌中のプロテオバクテリアの相対菌数（割合）を図４に、盲腸内細菌中のデスルフォビブリオの相対菌数（割合）を図５にそれぞれ示す。高脂肪食群において、ＧＲを含有する食餌を摂取した場合は、ＧＲを含有しない場合に比べて盲腸内におけるプロテオバクテリアの相対菌数が有意に小さかった。また、盲腸内の総菌数の測定値について各群間に有意な差はなかった。さらに、盲腸内におけるプロテオバクテリアの中でも最も多かったデスルフォビブリオの盲腸内における相対菌数は、高脂肪食群において、ＧＲを含有する食餌を摂取した場合は、ＧＲを含有しない場合に比べて有意に小さかった。また、通常食群においても、ＧＲを含有する食餌を摂取した場合は、ＧＲを含有しない場合に比べ、プロテオバクテリア及びデスルフォビブリオの盲腸内における相対菌数は、中央値が低値であった。これらの結果から、ＧＲを含有する食餌を摂取した場合は、腸内細菌叢におけるプロテオバクテリアの絶対数が小さくなることが分かる。さらに言えば、プロテオバクテリアの中でもデスルフォビブリオの絶対数が小さくなることが分かる。
全ての食餌群のマウスの盲腸内細菌におけるプロテオバクテリアの相対菌数（割合）と血漿ＬＰＳ濃度との関係を図６に示す。統計解析の結果、両者の間に有意な（ｐ＜０．０５）正の相関が認められ、ＧＲを含有する食餌を摂取した場合は、腸内細菌叢改善作用とともにＬＰＳ産生抑制作用が発揮されることが分かる。
なお、ＧＲの代謝物であり活性本体であると考えられているＳＦＮを用いた場合も、本実施例の結果と同様にＬＰＳ産生抑制作用及び腸内細菌叢改善作用を発揮すると推測される。
<Result>
The plasma LPS concentration of mice in each diet group is shown in FIG. In the high-fat diet group, when a diet containing GR was ingested, the plasma LPS concentration was significantly lower than that in the case not containing GR. From this result, it can be seen that the effect of suppressing LPS production by GR is more likely to be obtained in a state where LPS can be high.
The plasma LBP concentration of mice in each diet group is shown in FIG. In the high-fat diet group, when a diet containing GR was ingested, the plasma LBP concentration was significantly lower than that in the case not containing GR. From this result, it can be seen that the LBP suppressing effect by GR is more likely to be obtained in a state where the LBP can be a high value. Moreover, this result was in good agreement with the result of the plasma LPS concentration described above.
The cecal bacteria of mice in each diet group were measured at the portal level by intestinal flora analysis, and the relative number (ratio) of the relative bacteria is shown in FIG. 3, and the relative number (ratio) of proteobacteria in the cecal bacteria is shown. 4 shows the relative number (ratio) of desulfobibrio in the cecal bacteria, respectively, in FIG. In the high-fat diet group, when a diet containing GR was ingested, the relative number of proteobacteria in the cecum was significantly smaller than that in the case without GR. In addition, there was no significant difference between the groups in the measured values of the total number of bacteria in the cecum. Furthermore, the relative number of desulfovibrio in the cecum, which was the highest among the proteobacteria in the cecum, was significantly higher in the high-fat diet group when ingesting a diet containing GR than in the case without GR. It was small. In addition, even in the normal diet group, when a diet containing GR was ingested, the median relative number of proteobacteria and desulfovibrio in the cecum was lower than that in the case not containing GR. .. From these results, it can be seen that the absolute number of proteobacteria in the intestinal flora decreases when a diet containing GR is ingested. Furthermore, it can be seen that the absolute number of desulfovibrio among Proteobacteria is small.
FIG. 6 shows the relationship between the relative number (ratio) of proteobacteria in the cecal bacteria of mice of all diet groups and the plasma LPS concentration. As a result of statistical analysis, a significant (p <0.05) positive correlation was observed between the two, and when a diet containing GR was ingested, an effect of improving the intestinal flora and an effect of suppressing LPS production were exhibited. You can see that.
It is presumed that even when SFN, which is a metabolite of GR and is considered to be the active body, is used, it exerts an LPS production inhibitory effect and an intestinal bacterial flora improving effect as in the results of this example.
本発明により、腸内細菌叢を改善し、ＬＰＳの産生を抑制するという、ＧＲ及びＳＦＮの新たな用途が提供される。ＧＲ及び／又はＳＦＮを有効成分として含有する、本発明のＬＰＳ産生抑制剤、ＬＰＳ産生抑制用の食品組成物、腸内細菌叢改善剤、及び腸内細菌叢改善用の食品組成物は、ＬＰＳが高値であることに関連する疾患や病態の予防及び／又は改善に有用である。特に本発明の食品組成物は、機能性表示食品や特定保健用食品として消費者の健康志向にアピールするものとなり得る。 The present invention provides new uses for GR and SFN to improve the gut microbiota and suppress the production of LPS. The LPS production inhibitor, the food composition for suppressing LPS production, the intestinal flora improving agent, and the food composition for improving the intestinal flora, which contain GR and / or SFN as an active ingredient, are LPS. It is useful for the prevention and / or amelioration of diseases and pathological conditions associated with high values. In particular, the food composition of the present invention can appeal to consumers' health consciousness as a food with functional claims or a food for specified health use.
Claims (12)
それが有効成分として含有するのは、グルコラファニン（ＧＲ）及びスルフォラファン（ＳＦＮ）から選択される一以上であり、
前記血中ＬＰＳ濃度低下は、腸内におけるＬＰＳ産生が抑制されることによるものである。It is a blood LPS concentration lowering agent and
To contain it as an active ingredient state, and are one or more selected from glucoraphanin (GR) and sulforaphane (SFN),
The LPS concentration decreases in blood, Ru der due to LPS production in the intestine is suppressed.
それが有効成分として含有するのは、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上であり、
前記血中ＬＰＳ濃度低下は、腸内におけるＬＰＳ産生が抑制されることによるものである。It is a blood LPS concentration lowering agent and
It to contain as an active ingredient, Brassicaceae, Ri its extract or fraction thereof, and der one or more selected from the pulverized material,
The LPS concentration decreases in blood, Ru der due to LPS production in the intestine is suppressed.
前記アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物である。The agent of claim 2
The cruciferous plant, an extract thereof or a fraction thereof, and a crushed product thereof are seeds of broccoli sprout or broccoli, an extract thereof or a fraction thereof, and a crushed product thereof.
それが寄与成分として含有するのは、ＧＲ及びＳＦＮから選択される一以上であり、
前記血中ＬＰＳ濃度低下は、腸内におけるＬＰＳ産生が抑制されることによるものである。A food composition for lowering blood LPS concentration.
The it contains as contributing component state, and are one or more selected from GR and SFN,
The LPS concentration decreases in blood, Ru der due to LPS production in the intestine is suppressed.
それが寄与成分として含有するのは、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上であり、
前記血中ＬＰＳ濃度低下は、腸内におけるＬＰＳ産生が抑制されることによるものである。A food composition for lowering blood LPS concentration.
It to contain a contribution component, Brassicaceae state, and are one or more selected from the extract or a fraction thereof, and its pulverized product,
The LPS concentration decreases in blood, Ru der due to LPS production in the intestine is suppressed.
前記アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物である。The food composition of claim 5.
The cruciferous plant, an extract thereof or a fraction thereof, and a crushed product thereof are seeds of broccoli sprout or broccoli, an extract thereof or a fraction thereof, and a crushed product thereof.
それが有効成分として含有するのは、ＧＲ及びＳＦＮから選択される一以上であり、
前記血中ＬＰＳ濃度上昇抑制は、腸内におけるＬＰＳ産生が抑制されることによるもので ある。It is an inhibitor of blood LPS concentration increase,
It to contain as an active ingredient state, and are one or more selected from GR and SFN,
The blood concentration of LPS rise suppression Ru Oh due to LPS production in the intestine is suppressed.
それが有効成分として含有するのは、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上であり、
前記血中ＬＰＳ濃度上昇抑制は、腸内におけるＬＰＳ産生が抑制されることによるもので ある。It is an inhibitor of blood LPS concentration increase,
It to contain as an active ingredient, Brassicaceae, Ri its extract or fraction thereof, and der one or more selected from the pulverized material,
The blood concentration of LPS rise suppression Ru Oh due to LPS production in the intestine is suppressed.
前記アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物である。The agent of claim 8
The cruciferous plant, an extract thereof or a fraction thereof, and a crushed product thereof are seeds of broccoli sprout or broccoli, an extract thereof or a fraction thereof, and a crushed product thereof.
それが寄与成分として含有するのは、ＧＲ及びＳＦＮから選択される一以上であり、
前記血中ＬＰＳ濃度上昇抑制は、腸内におけるＬＰＳ産生が抑制されることによるもので ある。A food composition for suppressing an increase in blood LPS concentration.
The it contains as contributing component state, and are one or more selected from GR and SFN,
The blood concentration of LPS rise suppression Ru Oh due to LPS production in the intestine is suppressed.
それが寄与成分として含有するのは、アブラナ科植物、その抽出物又はその分画、及びその粉砕物から選択される一以上であり、
前記血中ＬＰＳ濃度上昇抑制は、腸内におけるＬＰＳ産生が抑制されることによるもので ある。A food composition for suppressing an increase in blood LPS concentration.
It to contain a contribution component, Brassicaceae state, and are one or more selected from the extract or a fraction thereof, and its pulverized product,
The blood concentration of LPS rise suppression Ru Oh due to LPS production in the intestine is suppressed.
前記アブラナ科植物、その抽出物又はその分画、及びその粉砕物は、ブロッコリースプラウト又はブロッコリーの種子、その抽出物又はその分画、及びその粉砕物である。
The food composition of claim 11.
The cruciferous plant, an extract thereof or a fraction thereof, and a crushed product thereof are seeds of broccoli sprout or broccoli, an extract thereof or a fraction thereof, and a crushed product thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020050613A JP6888145B2 (en) | 2020-03-23 | 2020-03-23 | LPS production inhibitor and food composition for suppressing LPS production |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020050613A JP6888145B2 (en) | 2020-03-23 | 2020-03-23 | LPS production inhibitor and food composition for suppressing LPS production |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2016065168A Division JP6710075B2 (en) | 2016-03-29 | 2016-03-29 | LPS production inhibitor and food composition for suppressing LPS production |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2020094071A JP2020094071A (en) | 2020-06-18 |
| JP6888145B2 true JP6888145B2 (en) | 2021-06-16 |
Family
ID=71085712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2020050613A Active JP6888145B2 (en) | 2020-03-23 | 2020-03-23 | LPS production inhibitor and food composition for suppressing LPS production |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP6888145B2 (en) |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5093938B2 (en) * | 1998-03-19 | 2012-12-12 | サンスター株式会社 | Bifidobacterium growth promoter, food and food material having bifidobacteria growth promoting action, and method for growing bifidobacteria |
| KR100845456B1 (en) * | 2001-02-06 | 2008-07-10 | 소시에떼 데 프로듀이 네슬레 소시에떼아노님 | Endotoxin binding by lactic acid bacteria and bifidobacteria |
-
2020
- 2020-03-23 JP JP2020050613A patent/JP6888145B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2020094071A (en) | 2020-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP6745250B2 (en) | Moringa extract | |
| US20070122508A1 (en) | Composition comprising the extract of actinidia arguta and related species for the prevention and treatment of allergic disease and non-allergic inflammatory disease | |
| US20120083525A1 (en) | Composition for preventing or treating obesity-related diseases mediated by the activation of ampk and including 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans as active ingredients | |
| JPWO2017094892A1 (en) | Health obesity maintenance agent | |
| WO1998013328A1 (en) | Cyclopentenones, process for preparing the same, and the use thereof | |
| JP5594819B2 (en) | Composition for improving lipid metabolism | |
| JP6710075B2 (en) | LPS production inhibitor and food composition for suppressing LPS production | |
| JP7007663B2 (en) | Kuro-moji extract | |
| JP7209193B2 (en) | Natural anticancer agent | |
| JP2024050702A (en) | Composition containing enterococcus faecalis as active ingredient for preventing or treating obesity or obesity-induced metabolic syndromes | |
| JP2016008180A (en) | Muscle endurance improver | |
| JP2009107965A (en) | Ceramide synthesis promoter, and external preparation for skin and food and drink | |
| KR101486484B1 (en) | A food composition for the improvement or prevention of asthma comprising extract of allium hookeri | |
| JP6888145B2 (en) | LPS production inhibitor and food composition for suppressing LPS production | |
| JP5710091B2 (en) | NO production promoter | |
| WO2020171144A1 (en) | Oral composition using clethra barbinervis containing biofunctional component in form of plant body | |
| JP2007031297A (en) | Skin-beautifying composition | |
| JP5000214B2 (en) | Novel compounds and osteoclast differentiation / proliferation inhibitors | |
| JP2017165686A (en) | Liver function improver | |
| CN106456685A (en) | Composition comprising extract of alpine wormwood | |
| KR20160056655A (en) | Composition for inhibiting obesity comprising complex salt of baicalin and zinc | |
| JP2019180412A (en) | Oral composition | |
| JP7499013B2 (en) | Melatonin production promoter and sleep quality improver | |
| JP2019176828A (en) | Oral composition | |
| JP7445689B2 (en) | lipolysis accelerator |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200323 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210309 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210409 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210518 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210519 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 6888145 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |