JP2021514993A - 悪液質および筋損失の予防、改善または治療用組成物 - Google Patents
悪液質および筋損失の予防、改善または治療用組成物 Download PDFInfo
- Publication number
- JP2021514993A JP2021514993A JP2020545175A JP2020545175A JP2021514993A JP 2021514993 A JP2021514993 A JP 2021514993A JP 2020545175 A JP2020545175 A JP 2020545175A JP 2020545175 A JP2020545175 A JP 2020545175A JP 2021514993 A JP2021514993 A JP 2021514993A
- Authority
- JP
- Japan
- Prior art keywords
- cachexia
- extract
- muscle
- muscle loss
- loss
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 210000003205 muscle Anatomy 0.000 title claims abstract description 82
- 206010006895 Cachexia Diseases 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims abstract description 26
- 238000011282 treatment Methods 0.000 title claims description 12
- 230000002265 prevention Effects 0.000 title claims description 7
- 239000000284 extract Substances 0.000 claims abstract description 85
- 239000004480 active ingredient Substances 0.000 claims abstract description 23
- 208000016261 weight loss Diseases 0.000 claims abstract description 12
- 230000004580 weight loss Effects 0.000 claims abstract description 12
- 230000003394 haemopoietic effect Effects 0.000 claims abstract description 8
- 231100000419 toxicity Toxicity 0.000 claims abstract description 7
- 230000001988 toxicity Effects 0.000 claims abstract description 7
- 241000736199 Paeonia Species 0.000 claims description 68
- 235000006484 Paeonia officinalis Nutrition 0.000 claims description 68
- 206010028980 Neoplasm Diseases 0.000 claims description 59
- 201000011510 cancer Diseases 0.000 claims description 23
- 235000013305 food Nutrition 0.000 claims description 20
- 230000001965 increasing effect Effects 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 230000001093 anti-cancer Effects 0.000 claims description 17
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- 239000002246 antineoplastic agent Substances 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical group O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 239000012153 distilled water Substances 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 3
- 239000012752 auxiliary agent Substances 0.000 claims description 3
- 206010061428 decreased appetite Diseases 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 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- 230000004596 appetite loss Effects 0.000 abstract description 10
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 230000000069 prophylactic effect Effects 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 34
- 230000000694 effects Effects 0.000 description 26
- 210000004027 cell Anatomy 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 208000006552 Lewis Lung Carcinoma Diseases 0.000 description 14
- 238000000034 method Methods 0.000 description 13
- 208000020816 lung neoplasm Diseases 0.000 description 12
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 11
- 230000037396 body weight Effects 0.000 description 11
- 201000005202 lung cancer Diseases 0.000 description 11
- 108090000695 Cytokines Proteins 0.000 description 10
- 102000004127 Cytokines Human genes 0.000 description 10
- 210000003141 lower extremity Anatomy 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 9
- 230000002757 inflammatory effect Effects 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 206010016256 fatigue Diseases 0.000 description 8
- 230000001939 inductive effect Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 208000019017 loss of appetite Diseases 0.000 description 7
- 235000021266 loss of appetite Nutrition 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000002671 adjuvant Substances 0.000 description 6
- 238000010171 animal model Methods 0.000 description 6
- 238000011394 anticancer treatment Methods 0.000 description 6
- 238000002512 chemotherapy Methods 0.000 description 6
- 235000005911 diet Nutrition 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 238000007918 intramuscular administration Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000001959 radiotherapy Methods 0.000 description 6
- 230000009182 swimming Effects 0.000 description 6
- 108090001005 Interleukin-6 Proteins 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 210000002966 serum Anatomy 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 4
- 208000030507 AIDS Diseases 0.000 description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 229920002527 Glycogen Polymers 0.000 description 4
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 4
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 4
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- 238000009395 breeding Methods 0.000 description 4
- 230000001488 breeding effect Effects 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 229960002949 fluorouracil Drugs 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229940096919 glycogen Drugs 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000004060 metabolic process Effects 0.000 description 4
- 230000004044 response Effects 0.000 description 4
- 239000006188 syrup Substances 0.000 description 4
- 235000020357 syrup Nutrition 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 240000004731 Acer pseudoplatanus Species 0.000 description 3
- 235000002754 Acer pseudoplatanus Nutrition 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 102100040669 F-box only protein 32 Human genes 0.000 description 3
- 101710191029 F-box only protein 32 Proteins 0.000 description 3
- 235000006485 Platanus occidentalis Nutrition 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 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 3
- 239000002775 capsule Substances 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
- 230000003247 decreasing effect Effects 0.000 description 3
- 230000037213 diet Effects 0.000 description 3
- 230000000378 dietary effect Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000007884 disintegrant Substances 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 235000001727 glucose Nutrition 0.000 description 3
- 238000010166 immunofluorescence Methods 0.000 description 3
- 206010025482 malaise Diseases 0.000 description 3
- 229940090004 megace Drugs 0.000 description 3
- RQZAXGRLVPAYTJ-GQFGMJRRSA-N megestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(C)=O)(OC(=O)C)[C@@]1(C)CC2 RQZAXGRLVPAYTJ-GQFGMJRRSA-N 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 235000018102 proteins Nutrition 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 235000000346 sugar Nutrition 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000001262 western blot Methods 0.000 description 3
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 102100021943 C-C motif chemokine 2 Human genes 0.000 description 2
- 101710155857 C-C motif chemokine 2 Proteins 0.000 description 2
- 208000017667 Chronic Disease Diseases 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 239000004375 Dextrin Substances 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- 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 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 2
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- MUMGGOZAMZWBJJ-DYKIIFRCSA-N Testostosterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 MUMGGOZAMZWBJJ-DYKIIFRCSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 230000001919 adrenal effect Effects 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 229940041181 antineoplastic drug Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 235000013361 beverage Nutrition 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 229960004316 cisplatin Drugs 0.000 description 2
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 229960003668 docetaxel Drugs 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 235000019197 fats Nutrition 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- HELXLJCILKEWJH-NCGAPWICSA-N rebaudioside A Chemical compound O([C@H]1[C@H](O)[C@@H](CO)O[C@H]([C@@H]1O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O HELXLJCILKEWJH-NCGAPWICSA-N 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000002639 sodium chloride Nutrition 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 201000008827 tuberculosis Diseases 0.000 description 2
- 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
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose 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-DCSYEGIMSA-N 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- 206010006002 Bone pain Diseases 0.000 description 1
- 241000178343 Butea superba Species 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 206010007733 Catabolic state Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 206010013911 Dysgeusia Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 239000004278 EU approved seasoning Substances 0.000 description 1
- 235000001911 Ehretia microphylla Nutrition 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000010228 Erectile Dysfunction Diseases 0.000 description 1
- 239000004386 Erythritol Substances 0.000 description 1
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 239000001512 FEMA 4601 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010019851 Hepatotoxicity Diseases 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 206010022489 Insulin Resistance Diseases 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 102000004889 Interleukin-6 Human genes 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 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
- 241001465754 Metazoa Species 0.000 description 1
- 102000008934 Muscle Proteins Human genes 0.000 description 1
- 108010074084 Muscle Proteins Proteins 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 244000236658 Paeonia lactiflora Species 0.000 description 1
- 235000008598 Paeonia lactiflora Nutrition 0.000 description 1
- 241001106477 Paeoniaceae Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- HELXLJCILKEWJH-SEAGSNCFSA-N Rebaudioside A Natural products O=C(O[C@H]1[C@@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@@]1(C)[C@@H]2[C@](C)([C@H]3[C@@]4(CC(=C)[C@@](O[C@H]5[C@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@@H](O[C@H]6[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O6)[C@H](O)[C@@H](CO)O5)(C4)CC3)CC2)CCC1 HELXLJCILKEWJH-SEAGSNCFSA-N 0.000 description 1
- 241000607768 Shigella Species 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- BCKXLBQYZLBQEK-KVVVOXFISA-M Sodium oleate Chemical compound [Na+].CCCCCCCC\C=C/CCCCCCCC([O-])=O BCKXLBQYZLBQEK-KVVVOXFISA-M 0.000 description 1
- 244000228451 Stevia rebaudiana Species 0.000 description 1
- 208000005718 Stomach Neoplasms Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 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
- 206010042674 Swelling Diseases 0.000 description 1
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 1
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 206010046788 Uterine haemorrhage Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 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
- 230000005856 abnormality Effects 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 230000001195 anabolic effect Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 208000022531 anorexia Diseases 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 229940124650 anti-cancer therapies Drugs 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000000022 bacteriostatic agent Substances 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- 235000012216 bentonite Nutrition 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-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
- 230000008512 biological response Effects 0.000 description 1
- 238000004159 blood analysis Methods 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007975 buffered saline Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 235000001046 cacaotero Nutrition 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 235000015897 energy drink Nutrition 0.000 description 1
- HELXLJCILKEWJH-UHFFFAOYSA-N entered according to Sigma 01432 Natural products C1CC2C3(C)CCCC(C)(C(=O)OC4C(C(O)C(O)C(CO)O4)O)C3CCC2(C2)CC(=C)C21OC(C1OC2C(C(O)C(O)C(CO)O2)O)OC(CO)C(O)C1OC1OC(CO)C(O)C(O)C1O HELXLJCILKEWJH-UHFFFAOYSA-N 0.000 description 1
- 235000019414 erythritol Nutrition 0.000 description 1
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 1
- 229940009714 erythritol Drugs 0.000 description 1
- 210000003743 erythrocyte Anatomy 0.000 description 1
- 201000004101 esophageal cancer Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 235000015203 fruit juice Nutrition 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 235000013376 functional food Nutrition 0.000 description 1
- 206010017758 gastric cancer Diseases 0.000 description 1
- 230000007661 gastrointestinal function Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000003958 hematopoietic stem cell Anatomy 0.000 description 1
- 230000007686 hepatotoxicity Effects 0.000 description 1
- 231100000304 hepatotoxicity Toxicity 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000001794 hormone therapy Methods 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 201000001881 impotence Diseases 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006193 liquid solution Substances 0.000 description 1
- 208000020442 loss of weight Diseases 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000004066 metabolic change Effects 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 208000013465 muscle pain Diseases 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000607 neurosecretory system Anatomy 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 239000000419 plant extract Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 229960004618 prednisone Drugs 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 235000019203 rebaudioside A Nutrition 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 108091008020 response regulators Proteins 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 201000011549 stomach cancer Diseases 0.000 description 1
- 208000003265 stomatitis Diseases 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Chemical group 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- 229960003604 testosterone Drugs 0.000 description 1
- 239000000892 thaumatin Substances 0.000 description 1
- 235000010436 thaumatin Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
Images
Classifications
-
- 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)
- A61K36/71—Ranunculaceae (Buttercup family), e.g. larkspur, hepatica, hydrastis, columbine or goldenseal
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/06—Anabolic agents
-
- 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
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
-
- 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)
- A61K36/65—Paeoniaceae (Peony family), e.g. Chinese peony
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- 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
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- 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
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/308—Foods, ingredients or supplements having a functional effect on health having an effect on cancer prevention
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
- A61K2236/30—Extraction of the material
- A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
- A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Botany (AREA)
- Mycology (AREA)
- Epidemiology (AREA)
- Medical Informatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Organic Chemistry (AREA)
- Microbiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Endocrinology (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
Description
シャクヤク(Paeoniae Radix)250gと30%エタノール2Lを3Lの反応槽に入れて、還流抽出器を用いて65℃で4時間還流抽出した。1次抽出物をろ過し、残渣物に再度30%エタノール2Lを添加して、同じ条件で2次抽出した。以後、2次抽出物をろ過して1次抽出物と混合した後、50℃以下で濃縮してエタノールを除去した。濃縮された抽出物を凍結乾燥させた後、ミキサで砕いて均質化した。抽出物の製造結果、乾燥重量43g(収率17.20%)のシャクヤク抽出物を得ることができた。
2−1.実験動物の準備および実験方法
実験動物は4週齢の雄C57BL/6マウス(18〜20g)で、中央実験動物(株)から供給されて実験動物飼育場で1週間適応させた後、実験に使用した。実験期間中、固形飼料と水は自由に摂取させ、飼育室の温度(22±2℃)、相対湿度(60±5%)と、明暗は12時間の周期を維持した。
腫瘍を誘導した後、14日間シャクヤク抽出物を経口投与しながらマウスの食事量を記録した。その結果、下記表1および図1Aと図5Aに開示されたように、腫瘍誘発群(対照群)対比のシャクヤク抽出物投与群で食事量が増加したことを確認することができた。下記表1中、*p<0.05;**p<0.01;および***p<0.001を示し、以下に記載の表および図面においても同じ意味で使用した。
腫瘍を誘導した後、14日間シャクヤク抽出物を経口投与した後、マウスを犠牲にして腫瘍の重量を確認した。その結果、下記表2および図1Bおよび図5Bに開示されたように、腫瘍誘発群(対照群)対比のシャクヤク抽出物投与群で有意な腫瘍の重量の変化は現れていないことが確認された。
腫瘍を誘導した後、14日間シャクヤク抽出物を経口投与した後、マウスを犠牲にして後ろ足筋肉の重量を確認した。その結果、下記表3および図1Cと図5Cに開示されたように、腫瘍誘発群(対照群)対比のシャクヤク抽出物投与群で有意な後ろ足筋肉の重量が増加したことが確認された。
腫瘍を誘導した後、14日間シャクヤク抽出物を経口投与した後、マウスを犠牲にして血清および筋肉内炎症性サイトカインの濃度を確認した。その結果、下記表4および図2と図8に開示されたように、正常群に比べて、対照群(腫瘍誘発群)で腫瘍によって炎症性サイトカインが増加し、対照群に比べて、シャクヤク抽出物投与群で有意に血清および筋肉内炎症性サイトカインが減少したことを確認して、シャクヤク抽出物の炎症および筋損失の改善効果を確認した。
腫瘍を誘導したマウスに既存の薬物またはシャクヤク抽出物を経口投与してから12日目に筋力(grip strength、g)および持久力(treadmill、sec)テストでマウスの筋力および持久力を確認した。測定結果、下記表5と表6および図3と図9に示すように、正常群と比較して、対照群では筋力および持久力が著しく減少したことを確認した。これに対し、対照群と比較して、シャクヤク抽出物投与群では筋力および持久力が有意に増加したことを確認して、腫瘍が誘導されたマウスの筋力および持久力が改善されたことが確認された。
腫瘍を誘導した後、14日間シャクヤク抽出物を経口投与した後、マウスを犠牲にしてLLC肺癌マウスの後ろ足筋肉内の筋肉分解因子(MAFbx)の減少効果を当業界で知られたウェスタンブロット(western blot)および免疫蛍光法(Immunofluorescence)を用いて測定した。測定結果、下記の図4に示すように、正常群と比較して、対照群では筋肉分解因子が著しく増加したことを確認した。これに対し、対照群と比較して、シャクヤク抽出物投与群では筋肉分解因子が有意に減少したことを確認した。
3−1.実験動物の準備
実験動物は4週齢の雄C57BL/6マウス(18〜20g)で、中央実験動物(株)から供給されて実験動物飼育場で1週間適応させた後、実験に使用した。実験期間中、固形飼料と水は自由に摂取させ、飼育室の温度(22±2℃)、相対湿度(60±5%)と、明暗は12時間の周期を維持した。
5−FU投与後、7日間シャクヤク抽出物(500mg/kg)を経口投与しながらマウスの体重と食事量を記録した。その結果、下記表7および図11Aと図11Bに開示されたように、正常群と比較して、対照群では体重と食事量が有意に減少するが、シャクヤク抽出物投与群では体重と食事量が回復することを確認することができた。
実験が終了した後、マウスの大腿部で筋肉を分離し、筋肉に存在するグリコーゲン成分(muscleglycogen)を当業界で知られた方法により測定した。
抗癌副作用を誘導したマウスにシャクヤク抽出物を経口投与してから6日目に強制遊泳試験でマウスの疲労度を確認し、マウス体重の5%程度を負荷した後、遊泳時間(swimming time)を測定した。
シャクヤク抽出物を7日間経口投与した後、マウスから血液を分離して血球分析器で分析した。分析結果、下記表10および図12に示すように、対照群(control)と比較して、シャクヤク抽出物投与群では白血球(white blood cell、WBC)およびリンパ球(lymphocyte)の数が有意に増加したことを確認することができた。また、シャクヤク抽出物投与群では、対照群と比較して血小板と赤血球数およびヘモグロビン数値が増加することが分かった。
Claims (7)
- シャクヤク(Paeoniae Radix)抽出物を有効成分として含む悪液質(cachexia)および筋損失の予防または治療用薬学的組成物。
- 前記シャクヤク抽出物は、蒸留水、C1〜C4の低級アルコール、ヘキサン、エチルアセテート、クロロホルム、ジエチルエーテル、ジクロロメタン、アセトンおよびこれらの混合物からなる群より選択される溶媒で抽出されるものである、請求項1に記載の悪液質および筋損失の予防または治療用薬学的組成物。
- 前記悪液質は、癌によって誘発されるものである、請求項1に記載の悪液質および筋損失の予防または治療用薬学的組成物。
- 前記悪液質は、抗癌剤によって誘発されるものである、請求項1に記載の悪液質および筋損失の予防または治療用薬学的組成物。
- 前記組成物は、食欲減少、体重減少、疲労度増加、炎症増加、筋肉損失および造血毒性からなる群より選択される症状を改善するものである、請求項1に記載の悪液質および筋損失の予防または治療用薬学的組成物。
- シャクヤク(Paeoniae Radix)抽出物を有効成分として含む悪液質および筋損失の予防または改善用食品組成物。
- 請求項1に記載の組成物を有効成分として含む抗癌補助剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20180024847 | 2018-02-28 | ||
KR10-2018-0024847 | 2018-02-28 | ||
PCT/KR2019/002446 WO2019168388A1 (ko) | 2018-02-28 | 2019-02-28 | 악액질 및 근손실 예방, 개선 또는 치료용 조성물 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2021514993A true JP2021514993A (ja) | 2021-06-17 |
JP7132344B2 JP7132344B2 (ja) | 2022-09-06 |
Family
ID=67805837
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020545175A Active JP7132344B2 (ja) | 2018-02-28 | 2019-02-28 | 悪液質および筋損失の予防、改善または治療用組成物 |
Country Status (6)
Country | Link |
---|---|
US (1) | US11684650B2 (ja) |
EP (1) | EP3760215A4 (ja) |
JP (1) | JP7132344B2 (ja) |
KR (1) | KR102166949B1 (ja) |
CN (2) | CN112040965B (ja) |
WO (1) | WO2019168388A1 (ja) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102392292B1 (ko) * | 2021-07-21 | 2022-05-03 | 중앙대학교 산학협력단 | 페오니플로린을 포함하는 악액질 및 근손실 예방 또는 치료용 조성물 |
CN113827624B (zh) * | 2021-09-29 | 2022-12-20 | 王�琦 | 一种榆黄蘑多糖及其应用 |
KR20230063915A (ko) * | 2021-10-29 | 2023-05-10 | 중앙대학교 산학협력단 | 근이영양증의 예방, 개선 또는 치료용 조성물 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009046391A (ja) * | 2005-07-06 | 2009-03-05 | Takehito Kono | 悪液質改善治療製剤および悪液質改善作用を有する食品製剤 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5936619A (ja) * | 1982-08-23 | 1984-02-28 | Tsumura Juntendo Inc | 制癌補助剤 |
US7534455B2 (en) * | 2000-03-09 | 2009-05-19 | Yale University | Herbal composition PHY906 and its use in chemotherapy |
JP5064630B2 (ja) * | 2000-03-09 | 2012-10-31 | エール ユニヴァーシティ | 薬草組成物phy906および化学療法におけるその使用 |
CN101347518B (zh) * | 2007-07-20 | 2012-06-27 | 天津天士力制药股份有限公司 | 一种赤芍的有效组分及其制备方法与用途 |
KR101133837B1 (ko) | 2010-03-10 | 2012-04-06 | 경희대학교 산학협력단 | 백두옹 추출물을 포함하는 항암제 부작용 억제용 조성물 |
JP5692785B2 (ja) * | 2010-12-09 | 2015-04-01 | 国立大学法人 鹿児島大学 | 悪液質改善剤 |
KR101332836B1 (ko) * | 2013-05-15 | 2013-11-27 | 재단법인 통합의료진흥원 | 자음강화탕을 포함하는 유방암 치료용 조성물 |
CN103301282B (zh) * | 2013-06-21 | 2015-06-17 | 成都中医药大学 | 一种治疗肌肉劳损的药物组合物及其制备方法和用途 |
KR101693828B1 (ko) * | 2015-10-30 | 2017-01-09 | 재단법인 통합의료진흥원 | 시호소간탕 추출물을 포함하는 신장암 또는 간암 치료용 조성물 |
-
2019
- 2019-02-28 JP JP2020545175A patent/JP7132344B2/ja active Active
- 2019-02-28 CN CN201980028639.1A patent/CN112040965B/zh active Active
- 2019-02-28 KR KR1020190023541A patent/KR102166949B1/ko active IP Right Grant
- 2019-02-28 EP EP19761453.0A patent/EP3760215A4/en active Pending
- 2019-02-28 CN CN202310254840.XA patent/CN116370527A/zh active Pending
- 2019-02-28 US US15/733,566 patent/US11684650B2/en active Active
- 2019-02-28 WO PCT/KR2019/002446 patent/WO2019168388A1/ko unknown
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009046391A (ja) * | 2005-07-06 | 2009-03-05 | Takehito Kono | 悪液質改善治療製剤および悪液質改善作用を有する食品製剤 |
Non-Patent Citations (2)
Title |
---|
CURRENT PHARMACEUTICAL BIOTECHNOLOGY, 2016, VOL.17, NO.13, PP.1147-1152, JPN6021038342, ISSN: 0004605707 * |
MEDIATORS OF INFLAMMATION, 2014, VOL.2014, ARTICLE NO.736563, PP.1-10, JPN6021038343, ISSN: 0004605706 * |
Also Published As
Publication number | Publication date |
---|---|
KR20190103987A (ko) | 2019-09-05 |
US11684650B2 (en) | 2023-06-27 |
EP3760215A4 (en) | 2022-01-12 |
EP3760215A1 (en) | 2021-01-06 |
CN112040965A (zh) | 2020-12-04 |
JP7132344B2 (ja) | 2022-09-06 |
CN116370527A (zh) | 2023-07-04 |
CN112040965B (zh) | 2023-04-14 |
US20210052688A1 (en) | 2021-02-25 |
KR102166949B1 (ko) | 2020-10-16 |
WO2019168388A1 (ko) | 2019-09-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR102188202B1 (ko) | 악액질 및 근손실 예방, 개선 또는 치료용 조성물 | |
JP7132344B2 (ja) | 悪液質および筋損失の予防、改善または治療用組成物 | |
KR101829637B1 (ko) | 참옻나무 목심 추출물을 함유하는 항암치료 부작용에 따른 소화기능장애, 백혈구 감소증 및 골수부전증의 개선, 예방 또는 치료용 조성물 | |
KR20210133909A (ko) | 함초 추출물을 포함하는 골 질환 또는 갱년기 질환의 예방 또는 치료용 조성물 | |
KR102203657B1 (ko) | 복합추출물을 함유하는 여성 항비만용 조성물 | |
KR101749967B1 (ko) | 콩 발아배아 추출물을 포함하는 비만의 예방 또는 치료용 약학 조성물 | |
KR20130083427A (ko) | Ppar 작용 조절 질환의 예방, 개선 또는 치료용 조성물 | |
KR102477343B1 (ko) | 한약복합추출물을 포함하는 악액질 예방 또는 치료용 조성물 | |
KR20190048431A (ko) | 백수오 조다당 추출물을 유효성분으로 함유하는 대장염의 예방, 개선 및 치료용 조성물 | |
KR102392292B1 (ko) | 페오니플로린을 포함하는 악액질 및 근손실 예방 또는 치료용 조성물 | |
KR102190001B1 (ko) | 천연물을 유효성분으로 포함하는 악액질 예방, 개선 또는 치료용 조성물 | |
JP2018135311A (ja) | Fgf21発現促進用組成物 | |
JP2019509994A (ja) | 芦根抽出物を有効成分として含む抗癌剤副作用による疾患の予防、改善または治療用組成物 | |
KR101181347B1 (ko) | 백선피 추출물을 유효성분으로 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 및 치료용 조성물 | |
KR101157214B1 (ko) | 속단 추출물을 유효성분으로 포함하는 지질 관련 심혈관 질환 또는 비만의 예방 및 치료용 조성물 | |
KR101578404B1 (ko) | 대극속 식물 추출물 또는 분획물을 유효성분으로 포함하는 암 예방 또는 치료용 조성물 | |
KR101241338B1 (ko) | 편축 추출물을 유효성분으로 함유하는 지질 관련 심혈관 질환 또는 비만의 예방 및 치료용 조성물 | |
KR102375935B1 (ko) | 피페린을 함유하는 암성 악액질 예방, 개선 또는 치료용 조성물 | |
WO2021112263A1 (ja) | アディポネクチン産生促進剤 | |
KR20180112561A (ko) | 노근 및 율초 추출물을 유효성분으로 하는 지방간, 고지혈증 및 변비 예방, 개선 또는 치료용 조성물 | |
JP2024528698A (ja) | ペオニフロリンを含む悪液質および筋損失の予防または治療用組成物 | |
KR101968398B1 (ko) | 면역계 부작용이 억제된 암치료용 약학 조성물 | |
KR20230173829A (ko) | 백미 추출물을 유효성분으로 포함하는 대사성 질환의 예방, 개선 또는 치료용 조성물 | |
KR20160059176A (ko) | 구척 추출물을 유효성분으로 함유하는 항암제 유도 조혈 독성의 예방 및 치료용 약학적 조성물 및 건강기능식품 | |
JP2023519549A (ja) | 炎症性疾患の治療または改善のための竜眼肉含有混合生薬抽出物を含む経口用組成物およびその使用 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20201021 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20211004 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211215 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220104 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220308 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20220711 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220714 |
|
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: 20220801 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20220825 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7132344 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |