JP5451403B2 - アドレノメデュリン産生増強剤 - Google Patents
アドレノメデュリン産生増強剤 Download PDFInfo
- Publication number
- JP5451403B2 JP5451403B2 JP2009554154A JP2009554154A JP5451403B2 JP 5451403 B2 JP5451403 B2 JP 5451403B2 JP 2009554154 A JP2009554154 A JP 2009554154A JP 2009554154 A JP2009554154 A JP 2009554154A JP 5451403 B2 JP5451403 B2 JP 5451403B2
- Authority
- JP
- Japan
- Prior art keywords
- administration
- adrenomedullin
- ginsenoside
- daikenchuto
- blood flow
- 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
- 102000004379 Adrenomedullin Human genes 0.000 title claims description 55
- 101800004616 Adrenomedullin Proteins 0.000 title claims description 55
- ULCUCJFASIJEOE-NPECTJMMSA-N adrenomedullin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)NCC(=O)N[C@@H]1C(N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)NCC(=O)N[C@H](C(=O)N[C@@H](CSSC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)[C@@H](C)O)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 ULCUCJFASIJEOE-NPECTJMMSA-N 0.000 title claims description 55
- 238000004519 manufacturing process Methods 0.000 title claims description 34
- 239000003623 enhancer Substances 0.000 title description 19
- BHHBIFKHVGSQFJ-UHFFFAOYSA-N Hydroxy-Sanshool Natural products CC=CC=CC=CCCC=CC=CC(=O)NC(C)(C)O BHHBIFKHVGSQFJ-UHFFFAOYSA-N 0.000 claims description 20
- GZYPWOGIYAIIPV-JBDTYSNRSA-N ginsenoside Rb1 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GZYPWOGIYAIIPV-JBDTYSNRSA-N 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 13
- YURJSTAIMNSZAE-HHNZYBFYSA-N ginsenoside Rg1 Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O YURJSTAIMNSZAE-HHNZYBFYSA-N 0.000 claims description 12
- 210000004369 blood Anatomy 0.000 claims description 11
- 239000008280 blood Substances 0.000 claims description 11
- 208000011231 Crohn disease Diseases 0.000 claims description 6
- 230000002708 enhancing effect Effects 0.000 claims description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 4
- 230000000968 intestinal effect Effects 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims 2
- 230000003449 preventive effect Effects 0.000 claims 1
- 230000000069 prophylactic effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 33
- 239000009372 dai-kenchu-to Substances 0.000 description 29
- 230000017531 blood circulation Effects 0.000 description 27
- 239000000284 extract Substances 0.000 description 26
- 239000000843 powder Substances 0.000 description 24
- 239000000523 sample Substances 0.000 description 23
- 238000012360 testing method Methods 0.000 description 21
- 241000700159 Rattus Species 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 12
- 235000020710 ginseng extract Nutrition 0.000 description 12
- 241000411851 herbal medicine Species 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- UFNDONGOJKNAES-UHFFFAOYSA-N Ginsenoside Rb1 Natural products CC(=CCCC(C)(OC1OC(COC2OC(CO)C(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CC(O)C45C)C UFNDONGOJKNAES-UHFFFAOYSA-N 0.000 description 11
- TXEWRVNOAJOINC-UHFFFAOYSA-N ginsenoside Rb2 Natural products CC(=CCCC(OC1OC(COC2OCC(O)C(O)C2O)C(O)C(O)C1O)C3CCC4(C)C3C(O)CC5C6(C)CCC(OC7OC(CO)C(O)C(O)C7OC8OC(CO)C(O)C(O)C8O)C(C)(C)C6CCC45C)C TXEWRVNOAJOINC-UHFFFAOYSA-N 0.000 description 11
- 230000001965 increasing effect Effects 0.000 description 11
- 238000005259 measurement Methods 0.000 description 11
- 241000208340 Araliaceae Species 0.000 description 10
- 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 10
- 235000003140 Panax quinquefolius Nutrition 0.000 description 10
- 239000012153 distilled water Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 235000008434 ginseng Nutrition 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- YUKQRDCYNOVPGJ-UHFFFAOYSA-N thioacetamide Chemical compound CC(N)=S YUKQRDCYNOVPGJ-UHFFFAOYSA-N 0.000 description 10
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 10
- OQWKEEOHDMUXEO-UHFFFAOYSA-N (6)-shogaol Natural products CCCCCC=CC(=O)CCC1=CC=C(O)C(OC)=C1 OQWKEEOHDMUXEO-UHFFFAOYSA-N 0.000 description 9
- OQWKEEOHDMUXEO-BQYQJAHWSA-N [6]-Shogaol Chemical compound CCCCC\C=C\C(=O)CCC1=CC=C(O)C(OC)=C1 OQWKEEOHDMUXEO-BQYQJAHWSA-N 0.000 description 9
- 210000002429 large intestine Anatomy 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- NHJVRSWLHSJWIN-UHFFFAOYSA-N 2,4,6-trinitrobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O NHJVRSWLHSJWIN-UHFFFAOYSA-N 0.000 description 8
- YURJSTAIMNSZAE-UHFFFAOYSA-N UNPD89172 Natural products C1CC(C2(CC(C3C(C)(C)C(O)CCC3(C)C2CC2O)OC3C(C(O)C(O)C(CO)O3)O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O YURJSTAIMNSZAE-UHFFFAOYSA-N 0.000 description 8
- 208000019425 cirrhosis of liver Diseases 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- CBEHEBUBNAGGKC-UHFFFAOYSA-N ginsenoside Rg1 Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C2C(O)CC4C5(C)CCC(O)C(C)(C)C5CC(OC6OC(CO)C(O)C(O)C6O)C34C)C CBEHEBUBNAGGKC-UHFFFAOYSA-N 0.000 description 8
- 239000008187 granular material Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 208000004232 Enteritis Diseases 0.000 description 7
- 201000004681 Psoriasis Diseases 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 239000005557 antagonist Substances 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- -1 etc. Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 6
- 244000000626 Daucus carota Species 0.000 description 6
- 235000002767 Daucus carota Nutrition 0.000 description 6
- 229920002674 hyaluronan Polymers 0.000 description 6
- 229960003160 hyaluronic acid Drugs 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical compound O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 description 5
- 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 5
- 210000004534 cecum Anatomy 0.000 description 5
- 238000013329 compounding Methods 0.000 description 5
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Natural products OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 description 5
- 239000003292 glue Substances 0.000 description 5
- LHFKHAVGGJJQFF-UHFFFAOYSA-N hydroxyl-alpha-sanshool Natural products CC=CC=CC=CCCC=CC(=O)NCC(C)(C)O LHFKHAVGGJJQFF-UHFFFAOYSA-N 0.000 description 5
- 229960002591 hydroxyproline Drugs 0.000 description 5
- 239000008101 lactose Substances 0.000 description 5
- 238000000034 method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Natural products ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 description 5
- 241000792859 Enema Species 0.000 description 4
- 206010016654 Fibrosis Diseases 0.000 description 4
- 229920001144 Hydroxy alpha sanshool Polymers 0.000 description 4
- SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 4
- 240000007594 Oryza sativa Species 0.000 description 4
- 235000007164 Oryza sativa Nutrition 0.000 description 4
- 239000004698 Polyethylene Substances 0.000 description 4
- 239000004743 Polypropylene Substances 0.000 description 4
- 230000036760 body temperature Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 210000001168 carotid artery common Anatomy 0.000 description 4
- 230000007882 cirrhosis Effects 0.000 description 4
- 210000001072 colon Anatomy 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 239000007920 enema Substances 0.000 description 4
- 229940095399 enema Drugs 0.000 description 4
- 208000006454 hepatitis Diseases 0.000 description 4
- 231100000283 hepatitis Toxicity 0.000 description 4
- 210000005240 left ventricle Anatomy 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 230000001338 necrotic effect Effects 0.000 description 4
- 230000001766 physiological effect Effects 0.000 description 4
- 229920000573 polyethylene Polymers 0.000 description 4
- 229920001155 polypropylene Polymers 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 230000029058 respiratory gaseous exchange Effects 0.000 description 4
- 235000009566 rice Nutrition 0.000 description 4
- 210000003437 trachea Anatomy 0.000 description 4
- LHFKHAVGGJJQFF-UMYNZBAMSA-N (2e,6e,8e,10e)-n-(2-hydroxy-2-methylpropyl)dodeca-2,6,8,10-tetraenamide Chemical compound C\C=C\C=C\C=C\CC\C=C\C(=O)NCC(C)(C)O LHFKHAVGGJJQFF-UMYNZBAMSA-N 0.000 description 3
- 208000020084 Bone disease Diseases 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 3
- 208000021908 Myocardial disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- PSKIOIDCXFHNJA-UHFFFAOYSA-N Sanshool Natural products CC=CC=CC=CCCC=CC=CC(=O)NC(C)C PSKIOIDCXFHNJA-UHFFFAOYSA-N 0.000 description 3
- 244000273928 Zingiber officinale Species 0.000 description 3
- 235000006886 Zingiber officinale Nutrition 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 206010013990 dysuria Diseases 0.000 description 3
- 235000008397 ginger Nutrition 0.000 description 3
- 229940002508 ginger extract Drugs 0.000 description 3
- 235000020708 ginger extract Nutrition 0.000 description 3
- 208000027866 inflammatory disease Diseases 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- 210000000056 organ Anatomy 0.000 description 3
- 239000002504 physiological saline solution Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- FBFMBWCLBGQEBU-GYMUUCMZSA-N 20-gluco-ginsenoside-Rf Natural products O([C@](CC/C=C(\C)/C)(C)[C@@H]1[C@H]2[C@H](O)C[C@H]3[C@](C)([C@]2(C)CC1)C[C@H](O[C@@H]1[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@H]1C(C)(C)[C@@H](O)CC[C@]31C)[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 FBFMBWCLBGQEBU-GYMUUCMZSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- 108010039627 Aprotinin Proteins 0.000 description 2
- 241000972773 Aulopiformes Species 0.000 description 2
- 208000031229 Cardiomyopathies Diseases 0.000 description 2
- SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 2
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- LHFKHAVGGJJQFF-UEOYEZOQSA-N Hydroxy-alpha-sanshool Chemical compound C\C=C\C=C\C=C/CC\C=C\C(=O)NCC(C)(C)O LHFKHAVGGJJQFF-UEOYEZOQSA-N 0.000 description 2
- PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- FADFGCOCHHNRHF-VAWYXSNFSA-N [10]-Shogaol Chemical compound CCCCCCCCC\C=C\C(=O)CCC1=CC=C(O)C(OC)=C1 FADFGCOCHHNRHF-VAWYXSNFSA-N 0.000 description 2
- 230000003187 abdominal effect Effects 0.000 description 2
- SBXYHCVXUCYYJT-UEOYEZOQSA-N alpha-Sanshool Chemical compound C\C=C\C=C\C=C/CC\C=C\C(=O)NCC(C)C SBXYHCVXUCYYJT-UEOYEZOQSA-N 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 210000000436 anus Anatomy 0.000 description 2
- 229960004405 aprotinin Drugs 0.000 description 2
- PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 2
- 125000000089 arabinosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)CO1)* 0.000 description 2
- SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 229960001484 edetic acid Drugs 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 230000002440 hepatic effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 210000004877 mucosa Anatomy 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- LLPWNQMSUYAGQI-UHFFFAOYSA-N notoginsenoside r1 Chemical compound C1CC(C2(CC(C3C(C)(C)C(O)CCC3(C)C2CC2O)OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)CO3)O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O LLPWNQMSUYAGQI-UHFFFAOYSA-N 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 238000001543 one-way ANOVA Methods 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 2
- 210000003240 portal vein Anatomy 0.000 description 2
- 208000002815 pulmonary hypertension Diseases 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000012207 quantitative assay Methods 0.000 description 2
- 235000019515 salmon Nutrition 0.000 description 2
- 238000013424 sirius red staining Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 230000013948 uterine smooth muscle contraction Effects 0.000 description 2
- 230000024883 vasodilation Effects 0.000 description 2
- RAQNTCRNSXYLAH-RFCGZQMISA-N (20S)-ginsenoside Rh1 Chemical compound O([C@@H]1[C@H]2C(C)(C)[C@@H](O)CC[C@]2(C)[C@H]2C[C@@H](O)[C@H]3[C@@]([C@@]2(C1)C)(C)CC[C@@H]3[C@@](C)(O)CCC=C(C)C)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O RAQNTCRNSXYLAH-RFCGZQMISA-N 0.000 description 1
- FBFMBWCLBGQEBU-RXMALORBSA-N (2s,3r,4s,5s,6r)-2-[(2r,3r,4s,5s,6r)-2-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-4,4,8,10,14-pentamethyl-17-[(2s)-6-methyl-2-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhept-5-en-2-yl]-2,3,5,6,7,9,11,12,13,15,16,17-dodecah Chemical compound O([C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(C[C@@H]([C@H]4C(C)(C)[C@@H](O)CC[C@]4(C)[C@H]3C[C@H]2O)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O[C@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)C)(C)CC1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O FBFMBWCLBGQEBU-RXMALORBSA-N 0.000 description 1
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- LGZSMXJRMTYABD-UHFFFAOYSA-N 8-shogaol Natural products CCCCCCCC=CC(=O)CCC1=CC=C(O)C(OC)=C1 LGZSMXJRMTYABD-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 235000005956 Cosmos caudatus Nutrition 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- 238000011891 EIA kit Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- LLPWNQMSUYAGQI-QBQUQATFSA-N Ginsenoside R1 Natural products O([C@](CC/C=C(\C)/C)(C)[C@@H]1[C@H]2[C@@H](O)C[C@H]3[C@](C)([C@]2(C)CC1)C[C@H](O[C@@H]1[C@H](O[C@@H]2[C@@H](O)[C@@H](O)[C@@H](O)CO2)[C@@H](O)[C@H](O)[C@@H](CO)O1)[C@H]1C(C)(C)[C@@H](O)CC[C@]31C)[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O1 LLPWNQMSUYAGQI-QBQUQATFSA-N 0.000 description 1
- AGBCLJAHARWNLA-DQUQINEDSA-N Ginsenoside RG2 Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@@](C)(O)CCC=C(C)C)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O AGBCLJAHARWNLA-DQUQINEDSA-N 0.000 description 1
- HYPFYJBWSTXDAS-UHFFFAOYSA-N Ginsenoside Rd Natural products CC(=CCCC(C)(OC1OC(CO)C(O)C(O)C1O)C2CCC3(C)C4CCC5C(C)(C)C(CCC5(C)C4CC(O)C23C)OC6OC(CO)C(O)C(O)C6OC7OC(CO)C(O)C(O)C7O)C HYPFYJBWSTXDAS-UHFFFAOYSA-N 0.000 description 1
- 206010019668 Hepatic fibrosis Diseases 0.000 description 1
- 101000690940 Homo sapiens Pro-adrenomedullin Proteins 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 241000233805 Phoenix Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 101100001053 Rattus norvegicus Adm gene Proteins 0.000 description 1
- 238000000692 Student's t-test Methods 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
- 238000001790 Welch's t-test Methods 0.000 description 1
- URPKGNJHPFKECW-MCQXXECASA-N [(2r,3s,4s,5r,6r)-6-[[(3s,5r,6s,8r,9r,10r,12r,13r,14r,17s)-3,12-dihydroxy-17-[(2s,5s)-5-(2-hydroxypropan-2-yl)-2-methyloxolan-2-yl]-4,4,8,10,14-pentamethyl-2,3,5,6,7,9,11,12,13,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-6-yl]oxy]-3,4-dihydroxy-5-[(2 Chemical compound C[C@@]1([C@@H]2[C@H]3[C@H](O)C[C@H]4[C@@]([C@@]3(CC2)C)(C)C[C@@H]([C@H]2C(C)(C)[C@@H](O)CC[C@@]24C)O[C@@H]2O[C@@H]([C@H]([C@H](O)[C@H]2O[C@H]2[C@@H]([C@@H](O)[C@H](O)CO2)O)O)COC(=O)C)CC[C@@H](C(C)(C)O)O1 URPKGNJHPFKECW-MCQXXECASA-N 0.000 description 1
- LGZSMXJRMTYABD-MDZDMXLPSA-N [8]-Shogaol Chemical compound CCCCCCC\C=C\C(=O)CCC1=CC=C(O)C(OC)=C1 LGZSMXJRMTYABD-MDZDMXLPSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- SBXYHCVXUCYYJT-UMYNZBAMSA-N beta-sanshool Chemical compound C\C=C\C=C\C=C\CC\C=C\C(=O)NCC(C)C SBXYHCVXUCYYJT-UMYNZBAMSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 230000013872 defecation Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 208000010643 digestive system disease Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000002158 endotoxin Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- KVUKDCFEXVWYBN-UHFFFAOYSA-N gamma-sanshooel Natural products CC=CC=CC=CCCC=CC=CC(=O)NCC(C)C KVUKDCFEXVWYBN-UHFFFAOYSA-N 0.000 description 1
- KVUKDCFEXVWYBN-JDXPBYPHSA-N gamma-sanshool Chemical compound C\C=C\C=C\C=C/CC\C=C\C=C\C(=O)NCC(C)C KVUKDCFEXVWYBN-JDXPBYPHSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001156 gastric mucosa Anatomy 0.000 description 1
- 229940089161 ginsenoside Drugs 0.000 description 1
- 229930182494 ginsenoside Natural products 0.000 description 1
- NODILNFGTFIURN-GZPRDHCNSA-N ginsenoside Rb2 Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1OC[C@H](O)[C@H](O)[C@H]1O NODILNFGTFIURN-GZPRDHCNSA-N 0.000 description 1
- JDCPEKQWFDWQLI-LUQKBWBOSA-N ginsenoside Rc Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)O[C@@](C)(CCC=C(C)C)[C@@H]1[C@@H]2[C@@]([C@@]3(CC[C@H]4C(C)(C)[C@@H](O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O[C@H]5[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O5)O)CC[C@]4(C)[C@H]3C[C@H]2O)C)(C)CC1)O[C@@H]1O[C@@H](CO)[C@H](O)[C@H]1O JDCPEKQWFDWQLI-LUQKBWBOSA-N 0.000 description 1
- PWAOOJDMFUQOKB-WCZZMFLVSA-N ginsenoside Re Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@H]1[C@H](O[C@@H]2[C@H]3C(C)(C)[C@@H](O)CC[C@]3(C)[C@@H]3[C@@]([C@@]4(CC[C@@H]([C@H]4[C@H](O)C3)[C@](C)(CCC=C(C)C)O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O3)O)C)(C)C2)O[C@H](CO)[C@@H](O)[C@@H]1O PWAOOJDMFUQOKB-WCZZMFLVSA-N 0.000 description 1
- AOGZLQUEBLOQCI-UHFFFAOYSA-N ginsenoside-Re Natural products CC1OC(OCC2OC(OC3CC4(C)C(CC(O)C5C(CCC45C)C(C)(CCC=C(C)C)OC6OC(CO)C(O)C(O)C6O)C7(C)CCC(O)C(C)(C)C37)C(O)C(O)C2O)C(O)C(O)C1O AOGZLQUEBLOQCI-UHFFFAOYSA-N 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 239000012676 herbal extract Substances 0.000 description 1
- 102000046663 human ADM Human genes 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 238000002350 laparotomy Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000007433 macroscopic evaluation Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 210000000713 mesentery Anatomy 0.000 description 1
- UHNSRFWQBVXBSK-UHFFFAOYSA-N methanol;2,2,2-trifluoroacetic acid Chemical compound OC.OC(=O)C(F)(F)F UHNSRFWQBVXBSK-UHFFFAOYSA-N 0.000 description 1
- 238000012806 monitoring device Methods 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 210000000754 myometrium Anatomy 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229940124595 oriental medicine Drugs 0.000 description 1
- 238000012335 pathological evaluation Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 208000018655 severe necrosis Diseases 0.000 description 1
- 238000007873 sieving Methods 0.000 description 1
- 238000004513 sizing Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 238000001694 spray drying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007447 staining method Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000010809 targeting technique Methods 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- OAHWPNUPCSDOGU-UHFFFAOYSA-N trans-10-shogaol Natural products CCCCCCCCCC=CC(=O)CCc1ccc(O)c(CO)c1 OAHWPNUPCSDOGU-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000007492 two-way ANOVA Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- UOJAEODBOCLNBU-UHFFFAOYSA-N vinaginsenoside R4 Natural products C1CC(C2(CC(O)C3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O UOJAEODBOCLNBU-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Classifications
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- 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
- A61K31/12—Ketones
-
- 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
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/164—Amides, e.g. hydroxamic acids of a carboxylic acid with an aminoalcohol, e.g. ceramides
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/575—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of three or more carbon atoms, e.g. cholane, cholestane, ergosterol, sitosterol
-
- 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)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/258—Panax (ginseng)
-
- 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)
- A61K36/75—Rutaceae (Rue family)
-
- 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)
- A61K36/906—Zingiberaceae (Ginger family)
- A61K36/9068—Zingiber, e.g. garden ginger
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J17/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, having an oxygen-containing hetero ring not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J17/005—Glycosides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J9/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane
Description
下記式(1)で表される化合物
と、下記式(2)で表される化合物および/または式(3)で表される化合物
とを有効成分として含有するアドレノメデュリン産生増強剤である。
大建中湯によるアドレノメデュリン産生増強作用:
SD系雄性ラット(8〜10週齢、体重300〜400g)を用いた(n=16)。蒸留水に膠飴を濃度480mg/mLとなるように添加して膠飴水溶液を調製した。この膠飴水溶液に、濃度60mg/mLとなるように、大建中湯エキス末を用時秤取して添加し30分間の室温攪拌にて均等分散して被験試料とした。37℃に保温した被験試料5mL/kgをカニューレを介し十二指腸内投与し、投与後0、15、30、60、90分後に門脈血を回収した。対照群には蒸留水を同様にして投与した。100μL量のエデト酸(EDTA)/アプロチニン(aprotinin)溶液(5mg EDTA−2Naと2500KIU aprotininを含有)を分注したポリプロピレン(PP)製15mL遠心管に約5mLの門脈血を採取し、1500g、4℃、15minの条件で遠心した。高速遠心機用PP製5mL遠心管に、2mL血漿と0.16mL量の下記組成の酸性化溶液を加え、血漿試料を酸性化させた。
大建中湯およびその構成生薬による血流増加作用:
SD系雄性ラット(9〜11週齢、体重260〜350g)を用いた(n=3または6)。蒸留水に膠飴160mg/mL、大建中湯エキス末20mg/mL濃度となるように膠飴および大建中湯エキス末を懸濁して被験試料(大建中湯)とした。また、人参エキス粉末、乾姜エキス粉末、山椒エキス粉末について、各生薬単独の被験試料を、蒸留水に、人参エキス粉末、乾姜エキス粉末、山椒エキス粉末をそれぞれ、濃度6mg/mL、10mg/mL、4mg/mLとなるように添加して調製した。さらに、上記3つの生薬のうち2つの生薬を併用した被験試料を、蒸留水に人参エキス粉末6mg/mLおよび乾姜エキス粉末10mg/mL、人参エキス粉末6mg/mLおよび山椒エキス粉末4mg/mL、山椒エキス粉末4mg/mLおよび乾姜エキス粉末10mg/mLの濃度となるように添加して調製した。37℃に保温した被験試料5mL/kgを予め盲腸より刺入し、結腸に留置した18Gサーフロー留置針を介し、手術後、血流のベース値が安定した0.5〜1時間後に結腸内投与した。
大建中湯の血流増加作用に対するADMアンタゴニスト前処置の影響:
SD系雄性ラットを、大建中湯投与群、ADMアンタゴニスト前処置群の2群に分けた(n=7ないし8)。蒸留水を用いて濃度膠飴160mg/mLの膠飴液を作製し、20mg/mL濃度になるように大建中湯エキス末を用時秤取し、同液中、30min間以上の室温攪拌にて均等分散して大建中湯(TJ−100)を調製した。大建中湯投与群に、これを900mg/5mL/kg量で結腸内投与した。一方、ADMアンタゴニスト前処置群は、ヒトADMアンタゴニスト(h.ADM22−52,Peptide社製4302−v)を生理食塩水内に30μmol/Lで溶解し、麻酔下で装着したカニューレから、30nmol/1mL/kgの用量で静脈内投与を行い、15分後、大建中湯を900mg/5mL/kg量で結腸内投与した。
生薬中の成分の血流増加作用(1):
SD系雄性ラット(8〜10週齢、体重240〜360g)を用いた(n=2ないし6)。1%Tween80水溶液にヒドロキシ−β−サンショオール、ジンセノシドRb1またはジンセノシドRg1を、それぞれ濃度0.06mg/mL、0.2mg/mL、0.2mg/mL濃度となるように添加して各生薬成分単独投与の被験試料とした。また、ヒドロキシサンショオールと、人参エキス、ジンセノシドRb1またはジンセノシドRg1との併用投与の被験試料について、1%Tween80水溶液に、濃度0.06mg/mLとなるヒドロキシサンショオールと、人参エキス粉末、ジンセノシドRb1またはジンセノシドRg1をそれぞれ濃度6mg/mL、0.2mg/mL、0.2mg/mLとなるように添加して調製した。37℃に保温した被験試料5mL/kgを予め盲腸より刺入し、結腸に留置した18Gサーフロー留置針を介し、手術後、血流のベース値が安定した0.5〜1時間後に結腸内投与した。対照群には1%Tween80水溶液を投与した。
生薬中の成分の血流増加作用(2):
SD系雄性ラット(8〜10週齢)を用いた。1%Tween80水溶液に、6−ショーガオールを濃度0.4mg/mLとなるよう添加して被験試料を調製した。また1%Tween80水溶液に、ジンセノシドRb1および6−ショーガオールをそれぞれ濃度0.2mg/mL、0.4mg/mLとなるよう添加して被験試料を調製した。37℃に保温した被験試料5mL/kgを予め盲腸より刺入し、結腸に留置した18Gサーフロー留置針を介し、手術後、血流のベース値が安定した0.5〜1時間後に結腸内投与した。対照群には1%Tween80水溶液を投与した。
クローン病動物モデルにおける抗腸炎作用:
BALB/c雄性マウス(20〜25g)を用いた(n=6または7)。蒸留水に膠飴および大建中湯エキス末をそれぞれ濃度80mg/mL、10mg/mL濃度になるように添加して被験試料(大建中湯)を調製した。
ラット肝硬変モデルにおける大建中湯の作用
SD系雄性ラットに対して、300 mg/L濃度のチオアセタミド(thioacetamide, TA)液を20週間飲水投与し、TA誘発の肝硬変を作製した。大建中湯エキス末は、TA処理開始から10週目より試験終了まで、50或いは200 mg/kg/day用量の混餌投与にて与えた。病態評価にあたっては、TA処理から10及び20週目に血液及び肝臓組織を採取した。採取した肝臓組織をヘマトキシリン・エオジン(HE)染色法とシリウスレッド染色法にて染色し、病理像を画像解析ソフト(Image J)に取り込み、肝繊維化を面積比にて評価した。血中ヒアルロン酸量は、ヒアルロン酸ELISAキット(コスモ・バイオ(株)社製)を用いて定量した。また、肝臓内のヒドロキシプロリン量の定量は、ノーマン・ローガン法により行った。
ジンセノシドRb1 50gおよびヒドロキシサンショオール 50gを乳糖270g、微結晶セルロース120g、およびステアリン酸マグネシウム10gと混合し、この混合物を単発式打錠機にて打錠して直径9mm、重量250mgの錠剤を製造した。
ジンセノシドRg1 25gとヒドロキシサンショオール25gをトウモロコシデンプン950gと混合し、水を加えて練合し、1mm×1mmの網目を有するスクリーンにて造粒、乾燥して顆粒剤とした。
ショーガオール50gとヒドロキシサンショオール50gを乳糖210g、でんぷん120g、滑石50g、ステアリン酸マグネシウム20gと混合し、250mgずつ硬カプセルに充填してカプセル剤を製造した。
人参エキス50gおよび山椒エキス50gを乳糖270g、微結晶セルロース120g、およびステアリン酸マグネシウム10gと混合し、この混合物を単発式打錠機にて打錠して直径9mm、重量250mgの錠剤を製造した。
人参エキス25gと山椒エキス25gおよび乾姜エキス25gをトウモロコシデンプン925gと混合し、水を加えて練合し、1mm×1mmの網目を有するスクリーンにて造粒、乾燥して顆粒剤とした。
大建中湯エキス顆粒の製造:
生薬を切裁し、人参3kg、山椒2kg、乾姜5kgを秤量・調合し、約12倍量の精製水に加え、撹拌しながら95〜100℃に昇温させ、昇温後、約60分間抽出した。抽出終了後、抽出液を固液分離し、分離液を減圧濃縮した後、固形分に対して1.0%に相当するショ糖脂肪酸エステルを添加混合し、噴霧乾燥により1.25kgの乾燥エキスを得た。該乾燥エキス1.25kgに対し10kgの膠飴(粉末飴)と乳糖3.7125kg、ステアリン酸マグネシウム 0.0375kgを添加して混合し、この混合物を常法により打錠機で錠剤に製した後、粉砕・整粒・篩別して良好な顆粒剤を得た。
Claims (3)
- ジンセノシドRb1及び/又はジンセノシドRg1と、ヒドロキシサンショールのみからなるアドレノメデュリン産生増強作用による腸管血流増加剤。
- ジンセノシドRb1及び/又はジンセノシドRg1と、ヒドロキシサンショールのみからなるアドレノメデュリン産生増強作用による炎症性腸疾患の予防・治療剤。
- 炎症性腸疾患が潰瘍性大腸炎またはクローン病である請求項2記載の予防・治療剤。
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/JP2008/052760 WO2009104248A1 (ja) | 2008-02-19 | 2008-02-19 | アドレノメデュリン産生増強剤 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013183789A Division JP2013241473A (ja) | 2013-09-05 | 2013-09-05 | アドレノメデュリン産生増強剤 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPWO2009104248A1 JPWO2009104248A1 (ja) | 2011-06-16 |
JP5451403B2 true JP5451403B2 (ja) | 2014-03-26 |
Family
ID=40985143
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009554154A Active JP5451403B2 (ja) | 2008-02-19 | 2008-02-19 | アドレノメデュリン産生増強剤 |
Country Status (6)
Country | Link |
---|---|
US (2) | US9193756B2 (ja) |
EP (1) | EP2243486B1 (ja) |
JP (1) | JP5451403B2 (ja) |
CN (1) | CN101945659A (ja) |
CA (1) | CA2715771C (ja) |
WO (1) | WO2009104248A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
TWI627972B (zh) * | 2013-05-10 | 2018-07-01 | 花王股份有限公司 | 浴用劑組合物 |
CN104229946B (zh) * | 2013-06-20 | 2017-02-08 | 罗民雄 | 一种可将纯净水制成电解水的简易电解方法 |
CN104622928A (zh) * | 2015-01-04 | 2015-05-20 | 中国药科大学 | 人参总皂苷通过激活IL-1β/IL-18活化分泌发挥免疫调节作用 |
AU2016324119B2 (en) * | 2015-09-18 | 2019-11-14 | Himuka AM Australia Pty Ltd. | Long-acting adrenomedullin derivative |
GB201901448D0 (en) * | 2019-02-01 | 2019-03-27 | Provost Fellows Found Scholars And The Other Members Of Board Of The College Of The Holy And Undivid | Adsorbent media |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07324039A (ja) * | 1994-05-31 | 1995-12-12 | Tsumura & Co | 一酸化窒素産生促進剤 |
JP2002145791A (ja) * | 2000-11-08 | 2002-05-22 | Tsumura & Co | 抗炎症性組成物 |
JP2007028997A (ja) * | 2005-07-27 | 2007-02-08 | Kanebo Seiyaku Kk | 生薬エキス配合流動食及びその使用 |
CN1994460A (zh) * | 2006-12-28 | 2007-07-11 | 刘光跃 | 治疗结肠炎的中药 |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS63137843A (ja) | 1986-11-29 | 1988-06-09 | Toshiba Corp | スクリ−ン印刷装置 |
JP2774769B2 (ja) | 1993-04-26 | 1998-07-09 | 賢治 寒川 | アドレノメデュリン |
US6440421B1 (en) | 1996-04-18 | 2002-08-27 | Auchkland Uniservices Limited | Treatment of bone disorders with adrenomedullin or adrenomedullin agonists |
JP4627574B2 (ja) * | 1999-05-18 | 2011-02-09 | 進 黒澤 | 消化管運動改善剤 |
WO2000078339A1 (fr) | 1999-06-23 | 2000-12-28 | Shionogi & Co., Ltd. | Inhibiteurs de contractions uterines |
ATE322284T1 (de) | 1999-06-23 | 2006-04-15 | Shionogi & Co | Adrenomedullin zur behandlung von störungen des harnlassens |
CN1364468A (zh) | 2001-01-19 | 2002-08-21 | 赵国林 | 中药材及配方的破壁提取方法 |
JP2003300899A (ja) | 2002-04-10 | 2003-10-21 | Shionogi & Co Ltd | 肺高血圧治療薬 |
JP4830093B2 (ja) | 2005-04-08 | 2011-12-07 | 国立大学法人 宮崎大学 | 非細菌性の炎症性疾患の予防又は治療剤 |
JP4505640B2 (ja) | 2005-04-12 | 2010-07-21 | 国立大学法人 宮崎大学 | 心筋障害の予防又は治療剤 |
CN100361705C (zh) | 2005-09-30 | 2008-01-16 | 中国科学院长春应用化学研究所 | 一种治疗慢性萎缩性胃炎的中药组合物 |
CN101069721A (zh) | 2006-05-09 | 2007-11-14 | 杜润 | 治疗心脏病的药物 |
-
2008
- 2008-02-19 CA CA2715771A patent/CA2715771C/en active Active
- 2008-02-19 WO PCT/JP2008/052760 patent/WO2009104248A1/ja active Application Filing
- 2008-02-19 CN CN2008801271342A patent/CN101945659A/zh active Pending
- 2008-02-19 JP JP2009554154A patent/JP5451403B2/ja active Active
- 2008-02-19 EP EP08720747.8A patent/EP2243486B1/en active Active
- 2008-02-19 US US12/918,437 patent/US9193756B2/en active Active
-
2015
- 2015-09-25 US US14/865,845 patent/US20160008385A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07324039A (ja) * | 1994-05-31 | 1995-12-12 | Tsumura & Co | 一酸化窒素産生促進剤 |
JP2002145791A (ja) * | 2000-11-08 | 2002-05-22 | Tsumura & Co | 抗炎症性組成物 |
JP2007028997A (ja) * | 2005-07-27 | 2007-02-08 | Kanebo Seiyaku Kk | 生薬エキス配合流動食及びその使用 |
CN1994460A (zh) * | 2006-12-28 | 2007-07-11 | 刘光跃 | 治疗结肠炎的中药 |
Non-Patent Citations (5)
Title |
---|
JPN6008016274; 日本臨床外科学会雑誌 vol.68, 2007, 370 * |
JPN6008016275; Murata, P et al: Life Sciences vol.70, 2002, 2061-2070 * |
JPN6008016276; Medical Science Digest vol.33, 2007, 753-756 * |
JPN6013012350; FAN,H. et al: 'Effects of four regulating-intestine prescriptions on pathology and ultrastructure of colon tissue i' World J Gastroenterol Vol.11, No.31, 2005, p.4800-6 * |
JPN6013012351; HAYAKAWA,T. et al: 'Effects of Dai-kenchu-to on intestinal obstruction following laparotomy' J Smooth Muscle Res Vol.35, No.2, 1999, p.47-54 * |
Also Published As
Publication number | Publication date |
---|---|
EP2243486B1 (en) | 2014-10-08 |
US9193756B2 (en) | 2015-11-24 |
WO2009104248A1 (ja) | 2009-08-27 |
EP2243486A4 (en) | 2012-05-09 |
CN101945659A (zh) | 2011-01-12 |
CA2715771C (en) | 2014-10-28 |
JPWO2009104248A1 (ja) | 2011-06-16 |
US20100331270A1 (en) | 2010-12-30 |
US20160008385A1 (en) | 2016-01-14 |
CA2715771A1 (en) | 2009-08-27 |
EP2243486A1 (en) | 2010-10-27 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
PL196015B1 (pl) | Zastosowanie ekstraktu roślinnego i nieterapeutyczny sposób hamowania łaknienia | |
US20160008385A1 (en) | Adrenomedullin production enhancer | |
JPH04504726A (ja) | アナフィラキシーの遅反応性物質に対する拮抗薬としてのリポキシンa↓4およびその誘導体の使用 | |
CN109675041A (zh) | 用于治疗癌症的系统、方法和制剂 | |
CN105935364B (zh) | 用于预防或治疗非酒精性肝病的包含人参皂苷f2的组合物 | |
WO2008122190A1 (fr) | Composition comprenant de la l-carnitine ou ses dérivés et son utilisation | |
TWI284038B (en) | Polyhydroxylated benzene-containing compounds | |
JP2008222656A (ja) | 肥満改善および予防用組成物ならびに健康食品 | |
CN100513415C (zh) | 胆汁酸衍生物及其医药用途 | |
KR102271821B1 (ko) | 오를리스타트 및 아커만시아 뮤시니필라 eb-amdk19 균주를 포함하는 조성물 | |
JP5671524B2 (ja) | 心血管障害の治療用医薬組成物及びその使用 | |
JP2013241473A (ja) | アドレノメデュリン産生増強剤 | |
WO2007088681A1 (ja) | グレリン産生促進剤 | |
ES2905407T3 (es) | Composiciones que contienen curcumina con biodisponibilidad mejorada | |
JP2018177739A (ja) | Trpa1活性化剤 | |
JP3717189B2 (ja) | 鎮痛抗炎症剤 | |
JP6603450B2 (ja) | 高脂血症および/または脂肪肝の改善剤 | |
US20230190682A1 (en) | Pharmaceutical composition for preventing or treating metabolic diseases | |
JPS5843385B2 (ja) | シジミの薬効成分及びその製造法 | |
JP3535207B2 (ja) | 抗ガン剤及びgrpレセプター拮抗剤 | |
JP7080504B2 (ja) | クルクミン含有経口摂取用固形製剤 | |
KR20230155649A (ko) | 리코칼콘 d 또는 이의 유사체를 포함하는 대사성 질환의 예방 또는 치료용 약학 조성물 | |
JPS62132822A (ja) | 肝炎治療剤 | |
KR20040036092A (ko) | 진세노사이드 Rh2 및 Rg3 항암 조성물 | |
JP2007084514A (ja) | 炎症性腸疾患用グリチルリチン製剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130319 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130513 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20130513 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130611 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130905 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20131022 |
|
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: 20131203 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20131226 |
|
R150 | Certificate of patent or registration of utility model |
Free format text: JAPANESE INTERMEDIATE CODE: R150 Ref document number: 5451403 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |