JP7209194B2 - 免疫チェックポイント抑制剤 - Google Patents
免疫チェックポイント抑制剤 Download PDFInfo
- Publication number
- JP7209194B2 JP7209194B2 JP2019528004A JP2019528004A JP7209194B2 JP 7209194 B2 JP7209194 B2 JP 7209194B2 JP 2019528004 A JP2019528004 A JP 2019528004A JP 2019528004 A JP2019528004 A JP 2019528004A JP 7209194 B2 JP7209194 B2 JP 7209194B2
- Authority
- JP
- Japan
- Prior art keywords
- immune checkpoint
- fermented
- checkpoint inhibitor
- lactic acid
- yeast
- 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
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 title claims description 37
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 title claims description 37
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 title claims description 37
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 title claims description 37
- 241000196324 Embryophyta Species 0.000 claims description 61
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 58
- 102100040678 Programmed cell death protein 1 Human genes 0.000 claims description 37
- 101710089372 Programmed cell death protein 1 Proteins 0.000 claims description 35
- 240000004808 Saccharomyces cerevisiae Species 0.000 claims description 31
- 239000004310 lactic acid Substances 0.000 claims description 29
- 235000014655 lactic acid Nutrition 0.000 claims description 29
- 235000014680 Saccharomyces cerevisiae Nutrition 0.000 claims description 28
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims description 27
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims description 27
- 206010028980 Neoplasm Diseases 0.000 claims description 26
- 230000014509 gene expression Effects 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 18
- 241000894006 Bacteria Species 0.000 claims description 17
- 235000013305 food Nutrition 0.000 claims description 14
- 108010074708 B7-H1 Antigen Proteins 0.000 claims description 13
- 102000008096 B7-H1 Antigen Human genes 0.000 claims description 13
- 239000004480 active ingredient Substances 0.000 claims description 12
- 244000062793 Sorghum vulgare Species 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 235000019713 millet Nutrition 0.000 claims description 9
- 235000008708 Morus alba Nutrition 0.000 claims description 8
- 240000000249 Morus alba Species 0.000 claims description 8
- 244000017020 Ipomoea batatas Species 0.000 claims description 7
- 235000002678 Ipomoea batatas Nutrition 0.000 claims description 7
- 241001474374 Blennius Species 0.000 claims description 6
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 6
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 6
- 241000219068 Actinidia Species 0.000 claims description 4
- 235000002732 Allium cepa var. cepa Nutrition 0.000 claims description 4
- 240000002234 Allium sativum Species 0.000 claims description 4
- 240000005528 Arctium lappa Species 0.000 claims description 4
- 235000003130 Arctium lappa Nutrition 0.000 claims description 4
- 235000008078 Arctium minus Nutrition 0.000 claims description 4
- 235000003261 Artemisia vulgaris Nutrition 0.000 claims description 4
- 240000006891 Artemisia vulgaris Species 0.000 claims description 4
- 241000512259 Ascophyllum nodosum Species 0.000 claims description 4
- 241000228212 Aspergillus Species 0.000 claims description 4
- 235000000832 Ayote Nutrition 0.000 claims description 4
- 240000002791 Brassica napus Species 0.000 claims description 4
- 235000011293 Brassica napus Nutrition 0.000 claims description 4
- 240000007124 Brassica oleracea Species 0.000 claims description 4
- 235000003899 Brassica oleracea var acephala Nutrition 0.000 claims description 4
- 235000011301 Brassica oleracea var capitata Nutrition 0.000 claims description 4
- 235000001169 Brassica oleracea var oleracea Nutrition 0.000 claims description 4
- 235000000540 Brassica rapa subsp rapa Nutrition 0.000 claims description 4
- 235000009467 Carica papaya Nutrition 0.000 claims description 4
- 240000006432 Carica papaya Species 0.000 claims description 4
- 241001070941 Castanea Species 0.000 claims description 4
- 235000014036 Castanea Nutrition 0.000 claims description 4
- 244000241235 Citrullus lanatus Species 0.000 claims description 4
- 235000012828 Citrullus lanatus var citroides Nutrition 0.000 claims description 4
- 241000951471 Citrus junos Species 0.000 claims description 4
- 244000175448 Citrus madurensis Species 0.000 claims description 4
- 241001672694 Citrus reticulata Species 0.000 claims description 4
- 235000007354 Coix lacryma jobi Nutrition 0.000 claims description 4
- 244000077995 Coix lacryma jobi Species 0.000 claims description 4
- 235000006481 Colocasia esculenta Nutrition 0.000 claims description 4
- 244000205754 Colocasia esculenta Species 0.000 claims description 4
- 235000009854 Cucurbita moschata Nutrition 0.000 claims description 4
- 235000009804 Cucurbita pepo subsp pepo Nutrition 0.000 claims description 4
- 235000003392 Curcuma domestica Nutrition 0.000 claims description 4
- 244000008991 Curcuma longa Species 0.000 claims description 4
- 241000371652 Curvularia clavata Species 0.000 claims description 4
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims description 4
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 claims description 4
- 235000002767 Daucus carota Nutrition 0.000 claims description 4
- 244000000626 Daucus carota Species 0.000 claims description 4
- 235000009008 Eriobotrya japonica Nutrition 0.000 claims description 4
- 244000061508 Eriobotrya japonica Species 0.000 claims description 4
- 235000017317 Fortunella Nutrition 0.000 claims description 4
- 244000194101 Ginkgo biloba Species 0.000 claims description 4
- 235000010469 Glycine max Nutrition 0.000 claims description 4
- 244000068988 Glycine max Species 0.000 claims description 4
- 235000007710 Grifola frondosa Nutrition 0.000 claims description 4
- 240000001080 Grifola frondosa Species 0.000 claims description 4
- 235000003230 Helianthus tuberosus Nutrition 0.000 claims description 4
- 240000008892 Helianthus tuberosus Species 0.000 claims description 4
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims description 4
- 240000005979 Hordeum vulgare Species 0.000 claims description 4
- 235000007340 Hordeum vulgare Nutrition 0.000 claims description 4
- 235000013719 Houttuynia cordata Nutrition 0.000 claims description 4
- 240000000691 Houttuynia cordata Species 0.000 claims description 4
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 4
- 240000000599 Lentinula edodes Species 0.000 claims description 4
- 241000234435 Lilium Species 0.000 claims description 4
- 244000070406 Malus silvestris Species 0.000 claims description 4
- 235000006508 Nelumbo nucifera Nutrition 0.000 claims description 4
- 240000002853 Nelumbo nucifera Species 0.000 claims description 4
- 235000007189 Oryza longistaminata Nutrition 0.000 claims description 4
- 240000007594 Oryza sativa Species 0.000 claims description 4
- 235000007164 Oryza sativa Nutrition 0.000 claims description 4
- 235000004347 Perilla Nutrition 0.000 claims description 4
- 244000124853 Perilla frutescens Species 0.000 claims description 4
- 235000003406 Polymnia sonchifolia Nutrition 0.000 claims description 4
- 244000134540 Polymnia sonchifolia Species 0.000 claims description 4
- 235000009827 Prunus armeniaca Nutrition 0.000 claims description 4
- 244000018633 Prunus armeniaca Species 0.000 claims description 4
- 235000006040 Prunus persica var persica Nutrition 0.000 claims description 4
- 235000006140 Raphanus sativus var sativus Nutrition 0.000 claims description 4
- 241000543810 Sasa veitchii Species 0.000 claims description 4
- 235000005187 Taraxacum officinale ssp. officinale Nutrition 0.000 claims description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 4
- 241001261506 Undaria pinnatifida Species 0.000 claims description 4
- 235000017190 Vitis vinifera subsp sylvestris Nutrition 0.000 claims description 4
- 244000237969 Vitis vulpina Species 0.000 claims description 4
- 235000017242 Vitis vulpina Nutrition 0.000 claims description 4
- 235000006886 Zingiber officinale Nutrition 0.000 claims description 4
- 244000273928 Zingiber officinale Species 0.000 claims description 4
- 241000235033 Zygosaccharomyces rouxii Species 0.000 claims description 4
- 235000001014 amino acid Nutrition 0.000 claims description 4
- 229940024606 amino acid Drugs 0.000 claims description 4
- 150000001413 amino acids Chemical class 0.000 claims description 4
- 235000007215 black sesame Nutrition 0.000 claims description 4
- 235000003373 curcuma longa Nutrition 0.000 claims description 4
- 229960003067 cystine Drugs 0.000 claims description 4
- 235000004611 garlic Nutrition 0.000 claims description 4
- 235000008397 ginger Nutrition 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- 235000014571 nuts Nutrition 0.000 claims description 4
- 150000007524 organic acids Chemical class 0.000 claims description 4
- 235000015136 pumpkin Nutrition 0.000 claims description 4
- 229940126585 therapeutic drug Drugs 0.000 claims description 4
- 235000013976 turmeric Nutrition 0.000 claims description 4
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 claims description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- 240000000425 Chaenomeles speciosa Species 0.000 claims description 3
- 235000005078 Chaenomeles speciosa Nutrition 0.000 claims description 3
- 240000008955 Dioscorea japonica Species 0.000 claims description 3
- 235000005251 Dioscorea japonica Nutrition 0.000 claims description 3
- 244000239348 Echinochloa crus galli var. praticola Species 0.000 claims description 3
- 235000011201 Ginkgo Nutrition 0.000 claims description 3
- 235000008100 Ginkgo biloba Nutrition 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004471 Glycine Substances 0.000 claims description 3
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 claims description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 3
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 3
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 3
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 claims description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 3
- 240000001929 Lactobacillus brevis Species 0.000 claims description 3
- 244000199866 Lactobacillus casei Species 0.000 claims description 3
- 240000006024 Lactobacillus plantarum Species 0.000 claims description 3
- 241000186612 Lactobacillus sakei Species 0.000 claims description 3
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 3
- 241000192130 Leuconostoc mesenteroides Species 0.000 claims description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 3
- 239000004472 Lysine Substances 0.000 claims description 3
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims description 3
- 235000017831 Pseudocydonia sinensis Nutrition 0.000 claims description 3
- 244000088415 Raphanus sativus Species 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- 244000057717 Streptococcus lactis Species 0.000 claims description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Substances 0.000 claims description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 3
- 235000004279 alanine Nutrition 0.000 claims description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 3
- 229960000310 isoleucine Drugs 0.000 claims description 3
- 239000001630 malic acid Substances 0.000 claims description 3
- 235000011090 malic acid Nutrition 0.000 claims description 3
- 229930182817 methionine Natural products 0.000 claims description 3
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 claims description 3
- 239000001384 succinic acid Substances 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- 239000004474 valine Substances 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 244000144730 Amygdalus persica Species 0.000 claims description 2
- 240000004244 Cucurbita moschata Species 0.000 claims description 2
- 235000013740 Juglans nigra Nutrition 0.000 claims description 2
- 240000007049 Juglans regia Species 0.000 claims description 2
- 241001134659 Lactobacillus curvatus Species 0.000 claims description 2
- 241000194036 Lactococcus Species 0.000 claims description 2
- 235000011430 Malus pumila Nutrition 0.000 claims description 2
- 235000015103 Malus silvestris Nutrition 0.000 claims description 2
- 241000237502 Ostreidae Species 0.000 claims description 2
- 241000192001 Pediococcus Species 0.000 claims description 2
- 241000191996 Pediococcus pentosaceus Species 0.000 claims description 2
- 235000014443 Pyrus communis Nutrition 0.000 claims description 2
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 claims description 2
- 235000009754 Vitis X bourquina Nutrition 0.000 claims description 2
- 235000012333 Vitis X labruscana Nutrition 0.000 claims description 2
- 240000006365 Vitis vinifera Species 0.000 claims description 2
- 235000014787 Vitis vinifera Nutrition 0.000 claims description 2
- 240000008866 Ziziphus nummularia Species 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 235000005985 organic acids Nutrition 0.000 claims description 2
- 235000020636 oyster Nutrition 0.000 claims description 2
- 230000001629 suppression Effects 0.000 claims description 2
- 244000291564 Allium cepa Species 0.000 claims 1
- 240000001987 Pyrus communis Species 0.000 claims 1
- 235000004976 Solanum vernei Nutrition 0.000 claims 1
- 241000352057 Solanum vernei Species 0.000 claims 1
- 240000001949 Taraxacum officinale Species 0.000 claims 1
- 235000011453 Vigna umbellata Nutrition 0.000 claims 1
- 240000001417 Vigna umbellata Species 0.000 claims 1
- 239000000047 product Substances 0.000 description 33
- 210000001541 thymus gland Anatomy 0.000 description 26
- 238000012360 testing method Methods 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 210000001744 T-lymphocyte Anatomy 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- 239000000523 sample Substances 0.000 description 14
- 239000003814 drug Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 238000000855 fermentation Methods 0.000 description 10
- 240000006439 Aspergillus oryzae Species 0.000 description 9
- 235000002247 Aspergillus oryzae Nutrition 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 239000000463 material Substances 0.000 description 9
- 210000000952 spleen Anatomy 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- 230000032683 aging Effects 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 235000013311 vegetables Nutrition 0.000 description 8
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 235000013399 edible fruits Nutrition 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 210000004698 lymphocyte Anatomy 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000011282 treatment Methods 0.000 description 7
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 6
- 244000046052 Phaseolus vulgaris Species 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 235000013339 cereals Nutrition 0.000 description 6
- 230000004151 fermentation Effects 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 210000003734 kidney Anatomy 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 206010003694 Atrophy Diseases 0.000 description 5
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 description 5
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 description 5
- 230000037444 atrophy Effects 0.000 description 5
- 238000009395 breeding Methods 0.000 description 5
- 230000001488 breeding effect Effects 0.000 description 5
- 238000000684 flow cytometry Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 239000007901 soft capsule Substances 0.000 description 5
- 235000019640 taste Nutrition 0.000 description 5
- 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 4
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 4
- 238000000018 DNA microarray Methods 0.000 description 4
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 description 4
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 102000011990 Sirtuin Human genes 0.000 description 4
- 108050002485 Sirtuin Proteins 0.000 description 4
- 239000002246 antineoplastic agent Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 201000001441 melanoma Diseases 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 235000021018 plums Nutrition 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 108020003175 receptors Proteins 0.000 description 4
- 102000005962 receptors Human genes 0.000 description 4
- 210000003289 regulatory T cell Anatomy 0.000 description 4
- -1 /or Species 0.000 description 3
- 241000234282 Allium Species 0.000 description 3
- 101100425600 Caenorhabditis elegans samp-1 gene Proteins 0.000 description 3
- 235000001715 Lentinula edodes Nutrition 0.000 description 3
- 235000006089 Phaseolus angularis Nutrition 0.000 description 3
- 241000220324 Pyrus Species 0.000 description 3
- 241000245665 Taraxacum Species 0.000 description 3
- 235000010711 Vigna angularis Nutrition 0.000 description 3
- 240000007098 Vigna angularis Species 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 239000012830 cancer therapeutic Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 230000001419 dependent effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 239000003651 drinking water Substances 0.000 description 3
- 235000020188 drinking water Nutrition 0.000 description 3
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 3
- 230000037406 food intake Effects 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 244000283763 Acetobacter aceti Species 0.000 description 2
- 102100032912 CD44 antigen Human genes 0.000 description 2
- 210000001239 CD8-positive, alpha-beta cytotoxic T lymphocyte Anatomy 0.000 description 2
- 108010021064 CTLA-4 Antigen Proteins 0.000 description 2
- 102000008203 CTLA-4 Antigen Human genes 0.000 description 2
- 229940045513 CTLA4 antagonist Drugs 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 241000219122 Cucurbita Species 0.000 description 2
- 235000011511 Diospyros Nutrition 0.000 description 2
- 101000937129 Drosophila melanogaster Cadherin-related tumor suppressor Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 101000868273 Homo sapiens CD44 antigen Proteins 0.000 description 2
- 101001078133 Homo sapiens Integrin alpha-2 Proteins 0.000 description 2
- 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 2
- 102100025305 Integrin alpha-2 Human genes 0.000 description 2
- 241000758791 Juglandaceae Species 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 235000015429 Mirabilis expansa Nutrition 0.000 description 2
- 244000294411 Mirabilis expansa Species 0.000 description 2
- 101100407308 Mus musculus Pdcd1lg2 gene Proteins 0.000 description 2
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 108700030875 Programmed Cell Death 1 Ligand 2 Proteins 0.000 description 2
- 102100024213 Programmed cell death 1 ligand 2 Human genes 0.000 description 2
- 240000005809 Prunus persica Species 0.000 description 2
- 241000235070 Saccharomyces Species 0.000 description 2
- 235000002595 Solanum tuberosum Nutrition 0.000 description 2
- 244000061456 Solanum tuberosum Species 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 241000219094 Vitaceae Species 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 241001247821 Ziziphus Species 0.000 description 2
- 241000235017 Zygosaccharomyces Species 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000021016 apples Nutrition 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 229960002685 biotin Drugs 0.000 description 2
- 235000020958 biotin Nutrition 0.000 description 2
- 239000011616 biotin Substances 0.000 description 2
- 235000008429 bread Nutrition 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000002619 cancer immunotherapy Methods 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000007910 chewable tablet Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 208000035250 cutaneous malignant susceptibility to 1 melanoma Diseases 0.000 description 2
- 210000004443 dendritic cell Anatomy 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 235000015203 fruit juice Nutrition 0.000 description 2
- 235000021021 grapes Nutrition 0.000 description 2
- 235000021384 green leafy vegetables Nutrition 0.000 description 2
- 210000002443 helper t lymphocyte Anatomy 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- 238000002350 laparotomy Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 235000013536 miso Nutrition 0.000 description 2
- 239000006072 paste Substances 0.000 description 2
- 235000011837 pasties Nutrition 0.000 description 2
- 235000021017 pears Nutrition 0.000 description 2
- 239000011574 phosphorus Substances 0.000 description 2
- 229910052698 phosphorus Inorganic materials 0.000 description 2
- 235000021110 pickles Nutrition 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 235000012015 potatoes Nutrition 0.000 description 2
- RADKZDMFGJYCBB-UHFFFAOYSA-N pyridoxal hydrochloride Natural products CC1=NC=C(CO)C(C=O)=C1O RADKZDMFGJYCBB-UHFFFAOYSA-N 0.000 description 2
- 230000000384 rearing effect Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 235000014347 soups Nutrition 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 235000019158 vitamin B6 Nutrition 0.000 description 2
- 239000011726 vitamin B6 Substances 0.000 description 2
- 229940011671 vitamin b6 Drugs 0.000 description 2
- 235000020234 walnut Nutrition 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- PJVXUVWGSCCGHT-ZPYZYFCMSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;(3s,4r,5r)-1,3,4,5,6-pentahydroxyhexan-2-one Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)C(=O)CO PJVXUVWGSCCGHT-ZPYZYFCMSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- 235000007847 Acetobacter aceti Nutrition 0.000 description 1
- 241000222518 Agaricus Species 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
- 238000012815 AlphaLISA Methods 0.000 description 1
- 241000122821 Aspergillus kawachii Species 0.000 description 1
- 241000228245 Aspergillus niger Species 0.000 description 1
- 244000206911 Candida holmii Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 208000005623 Carcinogenesis Diseases 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 241000190633 Cordyceps Species 0.000 description 1
- 235000017788 Cydonia oblonga Nutrition 0.000 description 1
- 244000281702 Dioscorea villosa Species 0.000 description 1
- 235000000504 Dioscorea villosa Nutrition 0.000 description 1
- 241000723267 Diospyros Species 0.000 description 1
- 244000236655 Diospyros kaki Species 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 235000009419 Fagopyrum esculentum Nutrition 0.000 description 1
- 240000008620 Fagopyrum esculentum Species 0.000 description 1
- 229920000855 Fucoidan Polymers 0.000 description 1
- 241000233866 Fungi Species 0.000 description 1
- 235000001637 Ganoderma lucidum Nutrition 0.000 description 1
- 240000008397 Ganoderma lucidum Species 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
- 239000012981 Hank's balanced salt solution Substances 0.000 description 1
- 208000017604 Hodgkin disease Diseases 0.000 description 1
- 208000021519 Hodgkin lymphoma Diseases 0.000 description 1
- 208000010747 Hodgkins lymphoma Diseases 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 235000009496 Juglans regia Nutrition 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 241000186604 Lactobacillus reuteri Species 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
- 241000192132 Leuconostoc Species 0.000 description 1
- 206010027480 Metastatic malignant melanoma Diseases 0.000 description 1
- 101001092200 Mus musculus RNA binding protein fox-1 homolog 3 Proteins 0.000 description 1
- 240000004371 Panax ginseng Species 0.000 description 1
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
- 235000003140 Panax quinquefolius Nutrition 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 102000003992 Peroxidases Human genes 0.000 description 1
- 238000002123 RNA extraction Methods 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 235000005733 Raphanus sativus var niger Nutrition 0.000 description 1
- 240000001970 Raphanus sativus var. sativus Species 0.000 description 1
- 208000006265 Renal cell carcinoma Diseases 0.000 description 1
- 229920002684 Sepharose Polymers 0.000 description 1
- 241000270295 Serpentes Species 0.000 description 1
- 102000039471 Small Nuclear RNA Human genes 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000005718 Stomach Neoplasms 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
- 239000002253 acid Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000003542 behavioural effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 235000019658 bitter taste Nutrition 0.000 description 1
- 230000036952 cancer formation Effects 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 239000008726 choto-san Substances 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000014510 cooky Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 239000008581 daisaikoto Substances 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 239000003534 dna topoisomerase inhibitor Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- CNNRFBWVTKFGRE-UHFFFAOYSA-N formic acid;2-oxopropanoic acid Chemical compound OC=O.CC(=O)C(O)=O CNNRFBWVTKFGRE-UHFFFAOYSA-N 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 230000005251 gamma ray Effects 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003832 immune regulation Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229940072221 immunoglobulins Drugs 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 231100000110 immunotoxic Toxicity 0.000 description 1
- 230000002625 immunotoxic effect Effects 0.000 description 1
- 231100000386 immunotoxicity Toxicity 0.000 description 1
- 230000007688 immunotoxicity Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229960005386 ipilimumab Drugs 0.000 description 1
- 239000009569 juzentaihoto Substances 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 208000006178 malignant mesothelioma Diseases 0.000 description 1
- 201000005282 malignant pleural mesothelioma Diseases 0.000 description 1
- HRLIOXLXPOHXTA-UHFFFAOYSA-N medetomidine Chemical compound C=1C=CC(C)=C(C)C=1C(C)C1=CN=C[N]1 HRLIOXLXPOHXTA-UHFFFAOYSA-N 0.000 description 1
- 229960002140 medetomidine Drugs 0.000 description 1
- 208000021039 metastatic melanoma Diseases 0.000 description 1
- DDLIGBOFAVUZHB-UHFFFAOYSA-N midazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NC=C2CN=C1C1=CC=CC=C1F DDLIGBOFAVUZHB-UHFFFAOYSA-N 0.000 description 1
- 229960003793 midazolam Drugs 0.000 description 1
- 210000000822 natural killer cell Anatomy 0.000 description 1
- 230000007230 neural mechanism Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 201000008968 osteosarcoma Diseases 0.000 description 1
- 235000016046 other dairy product Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 235000019685 rice crackers Nutrition 0.000 description 1
- 230000005070 ripening Effects 0.000 description 1
- 239000012488 sample solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 108091029842 small nuclear ribonucleic acid Proteins 0.000 description 1
- 235000014214 soft drink Nutrition 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 210000004367 thymic lymphocyte Anatomy 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013618 yogurt Nutrition 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/747—Lactobacilli, e.g. L. acidophilus or L. brevis
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/02—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation containing fruit or vegetable juices
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L11/00—Pulses, i.e. fruits of leguminous plants, for production of food; Products from legumes; Preparation or treatment thereof
- A23L11/05—Mashed or comminuted pulses or legumes; Products made therefrom
- A23L11/07—Soya beans, e.g. oil-extracted soya bean flakes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L11/00—Pulses, i.e. fruits of leguminous plants, for production of food; Products from legumes; Preparation or treatment thereof
- A23L11/50—Fermented pulses or legumes; Fermentation of pulses or legumes based on the addition of microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L19/00—Products from fruits or vegetables; Preparation or treatment thereof
- A23L19/20—Products from fruits or vegetables; Preparation or treatment thereof by pickling, e.g. sauerkraut or pickles
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
- A23L2/60—Sweeteners
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L2/00—Non-alcoholic beverages; Dry compositions or concentrates therefor; Their preparation
- A23L2/52—Adding ingredients
- A23L2/68—Acidifying substances
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L25/00—Food consisting mainly of nutmeat or seeds; Preparation or treatment thereof
- A23L25/40—Fermented products; Products treated with microorganisms or enzymes
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L29/00—Foods or foodstuffs containing additives; Preparation or treatment thereof
- A23L29/065—Microorganisms
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/135—Bacteria or derivatives thereof, e.g. probiotics
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/14—Yeasts or derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/40—Complete food formulations for specific consumer groups or specific purposes, e.g. infant formula
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L7/00—Cereal-derived products; Malt products; Preparation or treatment thereof
- A23L7/10—Cereal-derived products
- A23L7/104—Fermentation of farinaceous cereal or cereal material; Addition of enzymes or microorganisms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/06—Fungi, e.g. yeasts
- A61K36/062—Ascomycota
- A61K36/064—Saccharomycetales, e.g. baker's yeast
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
- A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Mycology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Microbiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Botany (AREA)
- Biotechnology (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Alternative & Traditional Medicine (AREA)
- Immunology (AREA)
- Agronomy & Crop Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Pediatric Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physiology (AREA)
- Medicines Containing Plant Substances (AREA)
- Preparation Of Fruits And Vegetables (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Edible Seaweed (AREA)
- Beans For Foods Or Fodder (AREA)
- Cereal-Derived Products (AREA)
- Non-Alcoholic Beverages (AREA)
Description
(a)大麦、黒大豆、赤米、黒米、小豆、はと麦、ヒエ、アワおよびキビよりなる群から選ばれる1種又は2種以上の豆・穀物類の麹菌発酵物
(b)ミカン、ブドウ、リンゴ、ヤマブドウ、モモ、カキ、パパイヤ、ナシ、スイカ、ウメ、イチジク、カリン、カボチャ、キンカン、ユズ、ビワ、アンズ、ナツメ、クリ、マタタビおよびスモモよりなる群から選ばれる1種又は2種以上の果実類の酵母および/又は乳酸菌発酵物
(c)紫イモ、菊芋、ニンジン、タマネギ、サツマイモ、里芋、自然薯、大根、赤カブ、ゴボウ、レンコン、ヤーコン、ユリ根、クワイ、しょうが、にんにくおよびウコンよりなる群から選ばれる1種又は2種以上の根菜類・イモ類の酵母および/又は乳酸菌発酵物
(d)キャベツ、紫蘇、桑葉、どくだみ、ヨモギ、クマザサおよびタンポポよりなる群から選ばれる1種又は2種以上の花・葉菜類の酵母および/又は乳酸菌発酵物
(e)コンブ、ワカメおよびモズクよりなる群から選ばれる1種又は2種以上の海藻類の酵母および/又は乳酸菌発酵物
(f)黒ゴマ、クルミおよびギンナンよりなる群から選ばれる1種又は2種以上の種子類の酵母および/又は乳酸菌発酵物
(g)マイタケおよびシイタケよりなる群から選ばれる1種又は2種のキノコ類の酵母および/又は乳酸菌発酵物
の混合物である植物発酵物を有効成分として含有することを特徴とする免疫チェックポイント抑制剤である。
(1)呈味性
果物、野菜等原料由来の甘味や有機酸に加え麹由来の甘味を有する。原料由来のポリフェノール類を含むものの苦味は少ない。
(2)水に対する溶解性
水に対して容易に溶解する。
(3)安定性
熱、酸に対して安定であり、ペーストは1年間室温保存しても腐敗や呈味性に変化はない。
(4)安全性
原料に用いた野菜、果物、ハーブ等は日常食しているものであり、また発酵に用いた酵母、乳酸菌、麹菌はいずれも食品の醸造や漬物等に由来する菌種を用いているため食経験が豊富である。
水分 15~35g
たんぱく質 5~20g
脂質 1~8g
灰分 1~5g
炭水化物 30~70g
ナトリウム 40~150mg
ビタミンB6 0.1~0.5mg
エネルギー 200~500kcal
アルギニン 0.2~0.6g
リジン 0.1~0.7g
ヒスチジン 0.1~0.4g
フェニルアラニン 0.2~0.8g
チロシン 0.1~0.6g
ロイシン 0.3~1.2g
イソロイシン 0.2~0.8g
メチオニン 0.05~0.3g
バリン 0.2~0.9g
アラニン 0.2~0.9g
グリシン 0.2~0.7g
プロリン 0.4~1.2g
グルタミン酸 1.2~3.0g
セリン 0.2~0.8g
スレオニン 0.2~0.7g
アスパラギン酸 0.4~1.5g
トリプトファン 0.03~0.15g
シスチン 0.05~0.40g
クエン酸 0.5~1.2g
リンゴ酸 0.05~0.5g
コハク酸 0.04~0.3g
乳酸 0.5~6.0g
ギ酸 0.01~0.1g
ピルビン酸 0.005~0.05g
遊離γ-アミノ酪酸 0.01~0.05g
リン 100~400mg
鉄 1~5mg
カルシウム 500~900mg
カリウム 600~1000mg
マグネシウム 70~120mg
亜鉛 0.8~1.6mg
ヨウ素 1.0~2.5mg
植物発酵物の製造:
以下の植物を原料として使用した。
(a)豆・穀類(大麦、黒大豆、赤米、黒米、小豆、はと麦、ヒエ、アワ、キビ)
(b)果実類(ミカン、ブドウ、リンゴ、ヤマブドウ、モモ、カキ、パパイヤ、ナシ、スイカ、ウメ、イチジク、カリン、カボチャ、キンカン、ユズ、ビワ、アンズ、ナツメ、クリ、マタタビ、スモモ)
(c)根菜類(紫イモ、菊芋、ニンジン、タマネギ、サツマイモ、里芋、自然薯、大根、赤カブ、ゴボウ、レンコン、ヤーコン、ユリ根、クワイ、しょうが、にんにく、ウコン)
(d)花・葉菜類(キャベツ、紫蘇、桑葉、どくだみ、ヨモギ、クマザサ、タンポポ)
(e)海草類(コンブ、ワカメ、モズク)
(f)種子類(黒ゴマ、クルミ、ギンナン)
(g)キノコ類(マイタケ、シイタケ)
(ア)一般分析値(100g当たり)
水分 25.2g
たんぱく質 11.8g
脂質 3.6g
灰分 2.1g
炭水化物 57.3g
ナトリウム 54.0mg
ビタミンB6 0.20mg
エネルギー 309kcal
試料を6規定塩酸で加水分解したものをアミノ酸自動分析計によって分析した。シスチンについては過蟻酸酸化処理後、塩酸加水分解を用いた。トリプトファンは高速液体クロマト法を用いた。
アルギニン 0.33g
リジン 0.34g
ヒスチジン 0.22g
フェニルアラニン 0.51g
チロシン 0.32g
ロイシン 0.74g
イソロイシン 0.42g
メチオニン 0.13g
バリン 0.54g
アラニン 0.48g
グリシン 0.42g
プロリン 0.92g
グルタミン酸 2.25g
セリン 0.4g
スレオニン 0.36g
アスパラギン酸 0.84g
トリプトファン 0.06g
シスチン 0.15g
クエン酸 0.81g
リンゴ酸 0.31g
コハク酸 0.12g
乳酸 1.17g
ギ酸 0.03g
ピルビン酸 0.01g
遊離γ-アミノ酪酸 24mg
リン 262mg
鉄 2.65mg
カルシウム 72.1mg
カリウム 798mg
マグネシウム 97.8mg
亜鉛 1.19mg
ヨウ素 1.7mg
胸腺の萎縮抑制試験:
(1)マウス
SAM-P1(♀)マウスは各群6匹で8週齢のものを三協ラボサービス株式会社から購入して使用した。飼育は、SPF仕様のマウス飼育施設(23±2℃、湿度50±10%、20:00~8:00の照明の明暗サイクル)を用い、マウスは各サンプル1群6匹を用い日本クレア製のポリカーボネートケージを用いSPF条件下で単独飼育した。餌は三協ラボサービスから購入した500N(γ線滅菌済)を自由摂取させた。床敷きは日本クレア製の高温殺菌済みを用いた。ケージ交換は週1回行った。なお、飼育中、マウスの摂餌量が減ることはなかった。
サンプルとして製造例1で製造したペースト状の植物発酵物を用いた。植物発酵物はイオン交換水に2.0%、0.2%。0%(対照)となるように溶解し、500ml容のメジウム瓶に分注したものを全てオートクレーブ滅菌(121℃、20分)し、生じた沈殿は給水瓶のノズルが詰らないように上清を無菌的に給水瓶(滅菌済)に移したものを供した。なお、植物発酵物の投与量は、植物発酵物を日常的に多めに摂取している事例(77g/週=11g/日)を参考にし、この30倍相当量を体重Kg当たりに換算して、算出された値である。この換算率は富山大学和漢医薬研究所において漢方薬類をマウスに適用する場合に経験的に用いられている数値である。(松本欣三 Personal Information第28回SAM研究会「老化モデル動物SAMP8の認知行動障害に対する漢方薬・釣藤散及び中薬・冠元顆粒の改善効果とそれらの神経機構」、5 July(2013) 愛知学院大学)。マウスが2.0%の濃度のサンプル30ml程度を1日で飲用した場合、ヒト換算だと約10g/日である。上記のようにしてイオン交換水で希釈した植物発酵物は飲水として自由摂取させた。
飼育2週目(10週齢)の若齢マウスと、飼育48週目(56週齢)の老齢マウスを、それぞれソムノペンチルで麻酔後、開腹し、胸腺、脾臓そして免疫に関与しない腎臓を採取しそれぞれの湿重量を計測した。図1に各群の胸腺の平均重量を示した。
老齢マウスの胸腺のみが加齢により萎縮を示し、若齢マウスの胸腺重量の約1/2となった。植物発酵物の0.2%群は0%群とほぼ同程度の胸腺重量であったが、2%群の結果を考慮すると濃度依存的に胸腺萎縮を抑制したが、10週齢の胸腺重量には達しなかった。このことは植物発酵物が免疫器官の高齢化による萎縮を抑制できることを示した。
フローサイトメトリー分析:
(1)マウス
SAMP-1(♂)マウスは各群8匹(1回目)または9匹(2回目)で8週齢のものを三協ラボサービス株式会社から購入して使用した。飼育は、試験例1と同様の施設および条件で単独飼育した。なお、飼育中、マウスの摂餌量が減ることはなかった。
サンプルとして製造例1で製造したペースト状の植物発酵物を用いた。植物発酵物の濃度を2.0%、0.4%。0%(対照)となるようにイオン交換水に溶解した以外は試験例1と同様に植物発酵物を飲水として自由摂取させた。
<1回目>
飼育2週目(10週齢)の若齢マウスを、3種混合麻酔薬(メデトミジン(0.3mg/0.3ml/Kg)、ミダゾラム(4mg/0.8ml/Kg)、プトルファノール(5mg/1ml/Kg):最終調整液量0.05ml/10g)を腹腔投与後、開腹し、下行動脈から全血、胸腺、脾臓を採取した。全血はそのまま冷蔵し、胸腺および脾臓はGibco社製の保存培地(AIM-V培地:血清フリー)に浸漬し、アイスパックとともに測定機関(株式会社鎌倉テクノサイエンス 生物試験事業部)に輸送した。
T cell(CD3e)
B cell(CD19)
NK cell(CD49b)
Regulatory T cell(CD4+CD25+)
PD-1+CD44+CD4+T cell
Helper T cell(CD4+CD8-)
CTL T cell(CD4-CD8+)
DP T cell(CD4+CD8+)
DN T cell(CD4-CD8-)
・CD45/CD3e/CD19/CD49b
・CD45/CD3e/CD4/CD8a/CD25/CD44/PD-1
PD-1および周辺のTregに注目した抗体(CD45, CD3e, CD4, CD8a, CD25、FoxP3およびCD279(PD-1))について行った。これらの細胞群を植物発酵物の濃度0%、0.4%、2.0%に分類し、更に担癌体と非担癌体に仕分けて解析した。担癌体におけるフローサイトメトリーによるPD-1+T細胞比率を表2に示した。
1) リンパ球中のT細胞の割合
2) リンパ球中のTreg細胞(CD3+,CD4+,CD25+,Fox3+)の割合
3) リンパ球中のPD-1陽性Treg細胞の割合
4) リンパ球中のCD4/PD-1陽性細胞の割合
5) T細胞中のHelper T細胞(CD3+、CD4+、CD8+)の割合
6) T細胞中のCTL(CD3+,CD4+, CD8+)の割合
7) T細胞中の PD-1 T細胞(CD3+,CD279(PD-1)+)の割合
DNAマイクロアレイ(免疫チェックポイントの遺伝子発現の解析):
植物発酵物0%(イオン交換水)あるいは2.0%を飲水として与えたSAMP-1(♂)マウス各群6匹について10週齢および56週齢まで長期飼育したマウスをソムノペンチル麻酔後、開腹し胸腺および腎臓を採取し、氷冷したRNA Later溶液に浸漬して、測定機関(フィルジェン株式会社)に冷蔵輸送した。RNA抽出からDNAマイクロアレイでの測定も測定機関によって行われた。
DNAマイクロアレイによる免疫チェックポイントの解析:
フローサイトメトリーの結果から免疫チェックポイントであるPD-1の関与が浮かび上がってきた。そこで、DNAマイクロアレイのプローブの中から免疫チェックポイントに関係するものを抽出する事を試みた。その結果、3種類が含まれていた。即ち、Ctla4(CTLA-4に相当)、Pdcd1(PD-L1に相当)およびCd274 (PD-1に相当)がデータベースに含まれていた。試験例3で得たデータの中から異なった視点からの再解析を行った。そこで胸腺並びに腎臓における10週齢vs56週齢、植物発酵物の濃度0%vs2.0%についての上記3遺伝子の遺伝子発現を比較した。胸腺のみ増減が見られ、腎臓は全く変化が無かった。胸腺の結果を表3に示した。
PD-1受容体とリガンド(PD-L1およびPD-L2)の結合阻害活性:
マウス由来のPD-1受容体に対するリガンド2種類、PD-L1およびPD-L2の結合試験が可能なビーピーエス バイオサイエンス社製の結合アッセイキットを使用し、in vitroの結合試験を実施した。検出方法は、パーキンエルマー製のAlphaLISA法で測定した。試験に用いた製造例1で製造した植物発酵物のペーストは茶褐色のためペルオキシダーゼによる発色方法は避けた。植物発酵物の10%水溶液をオートクレーブ殺菌し、エッペンドルフ遠心分離機で上清を回収した。なお、本サンプルは微量のビオチンを含むことから、PBSで洗浄したStrptoavidin Mag Sepharoseと混和することでサンプル中のビオチンを除去した。得られた水溶液を10%サンプル溶液と規定した。この溶液をmiliQ水で段階希釈して結合試験に供した。発色はパーキンエルマー製のOptiplate-384を用いて測定した。陽性コントロールとしてPD-1特異抗体を用いて結合阻害活性を確認した。
みそ様食品:
製造例1で製造したペースト状の植物発酵物とみそを混合し、調味料で味を調整してみそ様食品を製造した。
飲料:
製造例1で製造したペースト状の植物発酵物を水に溶解した後、果糖ブドウ糖液と果汁を混合し、味を調整して飲料を製造した。
ソフトカプセル:
製造例1で製造したペースト状の植物発酵物と、植物油、レシチンを混合したものを常法でソフトカプセルに充填してソフトカプセルを製造した。
チュアブル錠:
製造例1で製造したペースト状の植物発酵物と、結晶セルロース、白糖を混合したものを常法で打錠してチュアブル錠を製造した。
Claims (9)
- 次の(a)ないし(g)
(a)大麦、黒大豆、赤米、黒米、小豆、はと麦、ヒエ、アワおよびキビの麹菌発酵物
(b)ミカン、ブドウ、リンゴ、ヤマブドウ、モモ、カキ、パパイヤ、ナシ、スイカ、ウメ、イチジク、カリン、カボチャ、キンカン、ユズ、ビワ、アンズ、ナツメ、クリ、マタタビおよびスモモの酵母および/又は乳酸菌発酵物
(c)紫イモ、菊芋、ニンジン、タマネギ、サツマイモ、里芋、自然薯、大根、赤カブ、ゴボウ、レンコン、ヤーコン、ユリ根、クワイ、しょうが、にんにくおよびウコンの酵母および/又は乳酸菌発酵物
(d)キャベツ、紫蘇、桑葉、どくだみ、ヨモギ、クマザサおよびタンポポの酵母および/又は乳酸菌発酵物
(e)コンブ、ワカメおよびモズクの酵母および/又は乳酸菌発酵物
(f)黒ゴマ、クルミおよびギンナンの酵母および/又は乳酸菌発酵物
(g)マイタケおよびシイタケの酵母および/又は乳酸菌発酵物
の混合物である植物発酵物を有効成分として含有することを特徴とする免疫チェックポイント抑制剤。 - 植物発酵物が、植物発酵物100g当たり以下の組成のアミノ酸を含有するものである請求項1に記載の免疫チェックポイント抑制剤。
アルギニン 0.2~0.6g
リジン 0.1~0.7g
ヒスチジン 0.1~0.4g
フェニルアラニン 0.2~0.8g
チロシン 0.1~0.6g
ロイシン 0.3~1.2g
イソロイシン 0.2~0.8g
メチオニン 0.05~0.30g
バリン 0.2~0.9g
アラニン 0.2~0.9g
グリシン 0.2~0.7g
プロリン 0.4~1.2g
グルタミン酸 1.2~3.0g
セリン 0.2~0.8g
スレオニン 0.2~0.7g
アスパラギン酸 0.4~1.5g
トリプトファン 0.03~0.15g
シスチン 0.05~0.40g - 植物発酵物が、植物発酵物100g当たり以下の組成の有機酸を含有するものである請求項1又は2に記載の免疫チェックポイント抑制剤。
クエン酸 0.5~1.2g
リンゴ酸 0.05~0.5g
コハク酸 0.04~0.3g
乳酸 0.5~6.0g
ギ酸 0.01~0.1g
ピルビン酸 0.005~0.05g
遊離γ-アミノ酪酸 0.01~0.05g - 乳酸菌が、ぺディオコッカス・アシディラクティ(P.acidilacti)、ラクトバチルス・ブレビス(L. brevis)、ロイコノストック・メセンテロイデス(L. mesenteroides)、ラクトバチルス・プランタラム(L. plantarum)、ラクトコッカス・ラクチス(L. lactis)、ラクトバチルス・サケイ(L. sakei)、ペディオコッカス・ペントサセウス(P. pentosaceus)、ラクトバチルス・カゼイ(L. casei)およびラクトバチルス・クルバタス(L. curvatus)よりなる群から選ばれた1種または2種以上である請求項1~3のいずれかの項記載の免疫チェックポイント抑制剤。
- 酵母が、サッカロマイセス・セレビシエ(S. cervisiae)および/又はジゴサッカロマイセス・ロキシー(Z. rouxii)である請求項1~4のいずれかの項記載の免疫チェックポイント抑制剤。
- PD-1、PD-L1およびCTLA4から選ばれる1種以上の発現を抑制するものである請求項1~5のいずれかの項記載の免疫チェックポイント抑制剤。
- 更に、がんの治療薬および/またはがんの代替治療薬を含有する請求項1~6のいずれかの項記載の免疫チェックポイント抑制剤。
- 請求項1~7のいずれかの項記載の免疫チェックポイント抑制剤を含有する免疫チェックポイント抑制用飲食品。
- 医薬品である請求項1~7のいずれかの項記載の免疫チェックポイント抑制剤。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/JP2018/035179 WO2019009438A1 (ja) | 2018-09-21 | 2018-09-21 | 免疫チェックポイント抑制剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2019009438A1 JPWO2019009438A1 (ja) | 2021-08-19 |
JP7209194B2 true JP7209194B2 (ja) | 2023-01-20 |
Family
ID=64951035
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2019528004A Active JP7209194B2 (ja) | 2018-09-21 | 2018-09-21 | 免疫チェックポイント抑制剤 |
Country Status (4)
Country | Link |
---|---|
US (2) | US20220072068A1 (ja) |
EP (1) | EP3854224A4 (ja) |
JP (1) | JP7209194B2 (ja) |
WO (1) | WO2019009438A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN112334141A (zh) * | 2018-06-14 | 2021-02-05 | 株式会社明治 | 用于促进免疫检查点抑制疗法的组合物 |
CN110892984A (zh) * | 2019-10-17 | 2020-03-20 | 甘肃赛贝露生物科技有限责任公司 | 一种真空冷干燥活性红枣山药酵素粉 |
EP4176935A4 (en) * | 2020-06-29 | 2024-03-27 | Nihon Sizen Hakkoh Co Ltd | AGENT IMPROVING QUALITY OF LIFE |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016093104A1 (ja) | 2014-12-09 | 2016-06-16 | 株式会社日本自然発酵 | 老化抑制剤 |
Family Cites Families (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS6013670B2 (ja) | 1983-03-28 | 1985-04-09 | 大阪市 | ペルオキシダ−ゼの製造法 |
JPH09169661A (ja) * | 1995-10-18 | 1997-06-30 | Tannochiyou | ステロイドホルモン増加剤 |
JP2002138046A (ja) * | 2000-10-30 | 2002-05-14 | Toyo Shinyaku:Kk | Nk細胞活性化剤 |
WO2002072123A1 (fr) * | 2001-03-02 | 2002-09-19 | Beppu, Kunihide | Compositions prophylactiques ou therapeutiques pour des maladies tumorales ou liees au papillomavirus |
JP2004107286A (ja) * | 2002-09-20 | 2004-04-08 | Ichimaru Pharcos Co Ltd | 化粧料組成物及び美容・健康食品組成物 |
JP5102432B2 (ja) * | 2004-10-20 | 2012-12-19 | 株式会社創研 | がん細胞休眠剤 |
US20100003274A1 (en) * | 2005-03-04 | 2010-01-07 | Yuji Nonaka | Fermented compostions having immunodulatory actions |
JP4852683B2 (ja) * | 2005-09-26 | 2012-01-11 | 三和酒類株式会社 | 大麦を発酵に付したものを有効成分とする血管新生阻害の作用を有する組成物 |
JP5175442B2 (ja) * | 2006-03-03 | 2013-04-03 | 国立大学法人 香川大学 | ヤーコン由来の抗ガン剤 |
TWI306898B (en) * | 2006-06-02 | 2009-03-01 | Food Industry Res & Dev Inst | Fermented sesame meal composition and manufacturing method thereof |
JP5081485B2 (ja) * | 2007-04-05 | 2012-11-28 | 野田食菌工業株式会社 | 抗癌剤及び抗癌剤の製造方法 |
JP2013237652A (ja) * | 2012-05-16 | 2013-11-28 | Saido:Kk | パパイア発酵物を有効成分として含有する癌抑制組成物 |
JP2015202065A (ja) * | 2014-04-11 | 2015-11-16 | 株式会社 沖縄リサーチセンター | 発酵処理物並びにノビレチン及びタンゲレチン高含有率物の製造方法 |
WO2017167213A1 (en) * | 2016-03-30 | 2017-10-05 | Microbio Co., Ltd. | Combined cancer therapy with immune checkpoint modulators and fermentation products by symbiotic microbiota |
MX2019003447A (es) * | 2016-09-27 | 2019-08-29 | Univ Texas | Metodos para mejorar la terapia de bloqueo del punto de control inmune mediante la modulacion del microbioma. |
-
2018
- 2018-09-21 US US17/276,334 patent/US20220072068A1/en not_active Abandoned
- 2018-09-21 EP EP18827732.1A patent/EP3854224A4/en active Pending
- 2018-09-21 WO PCT/JP2018/035179 patent/WO2019009438A1/ja unknown
- 2018-09-21 JP JP2019528004A patent/JP7209194B2/ja active Active
-
2023
- 2023-10-11 US US18/484,738 patent/US20240041956A1/en active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2016093104A1 (ja) | 2014-12-09 | 2016-06-16 | 株式会社日本自然発酵 | 老化抑制剤 |
Also Published As
Publication number | Publication date |
---|---|
US20220072068A1 (en) | 2022-03-10 |
WO2019009438A1 (ja) | 2019-01-10 |
EP3854224A4 (en) | 2022-04-27 |
JPWO2019009438A1 (ja) | 2021-08-19 |
US20240041956A1 (en) | 2024-02-08 |
EP3854224A1 (en) | 2021-07-28 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20240041956A1 (en) | Immune checkpoint suppressant | |
JP4852683B2 (ja) | 大麦を発酵に付したものを有効成分とする血管新生阻害の作用を有する組成物 | |
JP5594819B2 (ja) | 脂質代謝改善用組成物 | |
US9700531B2 (en) | Composition comprising metformin as active ingredient for preventing or treating inflammatory bowel disease | |
WO2004112817A1 (ja) | セリ科植物由来抽出物およびその製造方法 | |
JP7209193B2 (ja) | 自然発がん予防剤 | |
JP6443804B2 (ja) | ナチュラルキラー細胞活性促進剤 | |
TWI784004B (zh) | 乙酸及/或乙酸鹽用以製造腦功能改善用組成物之用途 | |
WO2007018095A1 (ja) | ブナシメジ由来抽出物の製造方法 | |
KR101640284B1 (ko) | 메트포민과 퀘르세틴을 유효성분으로 함유하는 면역 질환의 예방 또는 치료용 조성물 | |
KR102244732B1 (ko) | 프로바이오틱 초산균인 아세토박터 파스테리아누스 mglv 및 이의 면역조절 효과 | |
Brito et al. | Nutritional, therapeutic, and technological perspectives of quinoa (Chenopodium quinoa Willd.): A review | |
EP1754473A1 (en) | Antitumor agent | |
JP2020014413A (ja) | 皮膚老化改善剤のスクリーニング方法 | |
TW200417366A (en) | Remedy | |
JP7206623B2 (ja) | 糖代謝異常の予防および改善用組成物 | |
JP7017749B2 (ja) | 抗アレルギー剤及びアレルギー疾患の予防又は治療用食品組成物 | |
RU2793287C2 (ru) | Кимчи для предотвращения или лечения связанных с helicobacter pylori заболеваний | |
JP2021500382A (ja) | 非アルコール性脂肪肝疾患の予防または改善用組成物 | |
JP7268812B2 (ja) | 抗肥満剤及び肥満の予防又は治療用食品組成物 | |
JP6736137B2 (ja) | 網膜保護組成物 | |
WO2022003749A1 (ja) | Qol改善剤 | |
JP7045661B2 (ja) | 免疫賦活組成物及び免疫賦活用食品組成物 | |
JP2022012264A (ja) | PPARγ2産生活性化剤、アディポネクチン産生活性化剤、及びMCP-1産生抑制剤 | |
KR20220109668A (ko) | 벼메뚜기 추출물을 포함하는 경구 투여용 조성물 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20210414 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220511 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220530 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220530 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220720 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220901 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20220901 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20220901 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20220922 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20220928 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20221109 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20221114 |
|
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: 20221130 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20221221 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7209194 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |