RU2717677C1 - Налмефен, налтрексон или их производные для применения в лечении (не)алкогольного стеатогепатита или неалкогольной жировой болезни печени - Google Patents
Налмефен, налтрексон или их производные для применения в лечении (не)алкогольного стеатогепатита или неалкогольной жировой болезни печени Download PDFInfo
- Publication number
- RU2717677C1 RU2717677C1 RU2018136387A RU2018136387A RU2717677C1 RU 2717677 C1 RU2717677 C1 RU 2717677C1 RU 2018136387 A RU2018136387 A RU 2018136387A RU 2018136387 A RU2018136387 A RU 2018136387A RU 2717677 C1 RU2717677 C1 RU 2717677C1
- Authority
- RU
- Russia
- Prior art keywords
- compound
- formula
- alcoholic
- nash
- alcoholic steatohepatitis
- Prior art date
Links
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 title claims abstract description 79
- 208000026594 alcoholic fatty liver disease Diseases 0.000 title claims abstract description 39
- 208000007082 Alcoholic Fatty Liver Diseases 0.000 title claims abstract description 38
- DQCKKXVULJGBQN-XFWGSAIBSA-N naltrexone Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=O)O)CC1)O)CC1CC1 DQCKKXVULJGBQN-XFWGSAIBSA-N 0.000 title claims description 14
- 229960003086 naltrexone Drugs 0.000 title claims description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims abstract description 53
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims abstract description 4
- 229910052760 oxygen Chemical group 0.000 claims abstract description 4
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract 2
- 239000001301 oxygen Chemical group 0.000 claims abstract 2
- 238000011282 treatment Methods 0.000 claims description 31
- 229940126062 Compound A Drugs 0.000 claims description 24
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims description 24
- 210000004185 liver Anatomy 0.000 claims description 24
- 230000002265 prevention Effects 0.000 claims description 16
- WJBLNOPPDWQMCH-MBPVOVBZSA-N Nalmefene Chemical compound N1([C@@H]2CC3=CC=C(C=4O[C@@H]5[C@](C3=4)([C@]2(CCC5=C)O)CC1)O)CC1CC1 WJBLNOPPDWQMCH-MBPVOVBZSA-N 0.000 claims description 15
- 229960005297 nalmefene Drugs 0.000 claims description 15
- 208000004930 Fatty Liver Diseases 0.000 claims description 7
- 206010000060 Abdominal distension Diseases 0.000 claims description 5
- 208000024330 bloating Diseases 0.000 claims description 5
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 5
- 208000006454 hepatitis Diseases 0.000 claims description 2
- 230000009467 reduction Effects 0.000 claims description 2
- 208000018191 liver inflammation Diseases 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 230000002829 reductive effect Effects 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 3
- 206010019668 Hepatic fibrosis Diseases 0.000 abstract 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 30
- 239000002158 endotoxin Substances 0.000 description 20
- 150000003839 salts Chemical class 0.000 description 17
- 238000000034 method Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 15
- 241000700159 Rattus Species 0.000 description 15
- 230000008818 liver damage Effects 0.000 description 15
- 206010067125 Liver injury Diseases 0.000 description 14
- 231100000234 hepatic damage Toxicity 0.000 description 14
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 description 14
- 231100000240 steatosis hepatitis Toxicity 0.000 description 13
- 230000007863 steatosis Effects 0.000 description 11
- 239000008194 pharmaceutical composition Substances 0.000 description 10
- 201000010099 disease Diseases 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- 210000001865 kupffer cell Anatomy 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 8
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 8
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 8
- 239000005537 C09CA07 - Telmisartan Substances 0.000 description 7
- 239000013543 active substance Substances 0.000 description 7
- 229960005187 telmisartan Drugs 0.000 description 7
- 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 6
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 6
- 102100031290 E3 UFM1-protein ligase 1 Human genes 0.000 description 6
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 6
- 101100155298 Homo sapiens UFL1 gene Proteins 0.000 description 6
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 6
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 6
- 230000037396 body weight Effects 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 208000010706 fatty liver disease Diseases 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 208000022309 Alcoholic Liver disease Diseases 0.000 description 5
- 206010016654 Fibrosis Diseases 0.000 description 5
- 238000011161 development Methods 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 235000019197 fats Nutrition 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 241000286209 Phasianidae Species 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000006378 damage Effects 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000004761 fibrosis Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 4
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 description 4
- LFULEKSKNZEWOE-UHFFFAOYSA-N propanil Chemical compound CCC(=O)NC1=CC=C(Cl)C(Cl)=C1 LFULEKSKNZEWOE-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000037487 Endotoxemia Diseases 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 238000013231 NASH rodent model Methods 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004027 cell Anatomy 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
- 230000008021 deposition Effects 0.000 description 3
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 238000001000 micrograph Methods 0.000 description 3
- -1 morphinane chemical compounds Chemical class 0.000 description 3
- 238000000465 moulding Methods 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 241000272517 Anseriformes Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 102000008186 Collagen Human genes 0.000 description 2
- 108010035532 Collagen Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 241000287828 Gallus gallus Species 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010019708 Hepatic steatosis Diseases 0.000 description 2
- 206010022489 Insulin Resistance Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 235000013330 chicken meat Nutrition 0.000 description 2
- 229960001231 choline Drugs 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 230000007882 cirrhosis Effects 0.000 description 2
- 229920001436 collagen Polymers 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 238000002716 delivery method Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 229950001279 elafibranor Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- AFLFKFHDSCQHOL-IZZDOVSWSA-N gft505 Chemical compound C1=CC(SC)=CC=C1C(=O)\C=C\C1=CC(C)=C(OC(C)(C)C(O)=O)C(C)=C1 AFLFKFHDSCQHOL-IZZDOVSWSA-N 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
- 235000009200 high fat diet Nutrition 0.000 description 2
- 230000028709 inflammatory response Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000005229 liver cell Anatomy 0.000 description 2
- 210000005228 liver tissue Anatomy 0.000 description 2
- 239000001630 malic acid Substances 0.000 description 2
- 235000011090 malic acid Nutrition 0.000 description 2
- 229940099690 malic acid Drugs 0.000 description 2
- 244000005706 microflora Species 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229940005483 opioid analgesics Drugs 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 238000001050 pharmacotherapy Methods 0.000 description 2
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 2
- 210000003240 portal vein Anatomy 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000000770 proinflammatory effect Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 210000003491 skin Anatomy 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000035882 stress Effects 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- RUDATBOHQWOJDD-UHFFFAOYSA-N (3beta,5beta,7alpha)-3,7-Dihydroxycholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 RUDATBOHQWOJDD-UHFFFAOYSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical group C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000271566 Aves Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000004481 Choline Deficiency Diseases 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 206010009208 Cirrhosis alcoholic Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000010334 End Stage Liver Disease Diseases 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 206010027940 Mood altered Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 235000021314 Palmitic acid Nutrition 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 108010020346 Polyglutamic Acid Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000287530 Psittaciformes Species 0.000 description 1
- 101000918775 Rattus norvegicus Malonyl-CoA decarboxylase, mitochondrial Proteins 0.000 description 1
- 208000004756 Respiratory Insufficiency Diseases 0.000 description 1
- 206010038678 Respiratory depression Diseases 0.000 description 1
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 241000287231 Serinus Species 0.000 description 1
- YIQKLZYTHXTDDT-UHFFFAOYSA-H Sirius red F3B Chemical compound C1=CC(=CC=C1N=NC2=CC(=C(C=C2)N=NC3=C(C=C4C=C(C=CC4=C3[O-])NC(=O)NC5=CC6=CC(=C(C(=C6C=C5)[O-])N=NC7=C(C=C(C=C7)N=NC8=CC=C(C=C8)S(=O)(=O)[O-])S(=O)(=O)[O-])S(=O)(=O)O)S(=O)(=O)O)S(=O)(=O)[O-])S(=O)(=O)[O-].[Na+].[Na+].[Na+].[Na+].[Na+].[Na+] YIQKLZYTHXTDDT-UHFFFAOYSA-H 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- ZSJLQEPLLKMAKR-UHFFFAOYSA-N Streptozotocin Natural products O=NN(C)C(=O)NC1C(O)OC(CO)C(O)C1O ZSJLQEPLLKMAKR-UHFFFAOYSA-N 0.000 description 1
- 241000272534 Struthio camelus Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 210000001789 adipocyte Anatomy 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 208000010002 alcoholic liver cirrhosis Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003472 antidiabetic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 229960003237 betaine Drugs 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000015895 biscuits Nutrition 0.000 description 1
- 238000009534 blood test Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 208000021752 choline deficiency disease Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 208000011444 chronic liver failure Diseases 0.000 description 1
- 229960004106 citric acid Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 231100000284 endotoxic Toxicity 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229960002598 fumaric acid Drugs 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000002008 hemorrhagic effect Effects 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 230000002443 hepatoprotective effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000006749 inflammatory damage Effects 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 210000005027 intestinal barrier Anatomy 0.000 description 1
- 230000007358 intestinal barrier function Effects 0.000 description 1
- 210000005026 intestinal epithelial barrier Anatomy 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000012317 liver biopsy Methods 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 description 1
- 229960003105 metformin Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 210000000274 microglia Anatomy 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- 230000007510 mood change Effects 0.000 description 1
- INAXVFBXDYWQFN-XHSDSOJGSA-N morphinan Chemical class C1C2=CC=CC=C2[C@]23CCCC[C@H]3[C@@H]1NCC2 INAXVFBXDYWQFN-XHSDSOJGSA-N 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical compound C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 229940098695 palmitic acid Drugs 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000006461 physiological response Effects 0.000 description 1
- 229960005095 pioglitazone Drugs 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 244000144977 poultry Species 0.000 description 1
- 235000013594 poultry meat Nutrition 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 229910052711 selenium Inorganic materials 0.000 description 1
- 239000011669 selenium Substances 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- ZSJLQEPLLKMAKR-GKHCUFPYSA-N streptozocin Chemical compound O=NN(C)C(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O ZSJLQEPLLKMAKR-GKHCUFPYSA-N 0.000 description 1
- 229960001052 streptozocin Drugs 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 230000005945 translocation Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- RUDATBOHQWOJDD-UZVSRGJWSA-N ursodeoxycholic acid Chemical compound C([C@H]1C[C@@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)CC1 RUDATBOHQWOJDD-UZVSRGJWSA-N 0.000 description 1
- 229960001661 ursodiol Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Gastroenterology & Hepatology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662326435P | 2016-04-22 | 2016-04-22 | |
| US62/326,435 | 2016-04-22 | ||
| US201662395436P | 2016-09-16 | 2016-09-16 | |
| US62/395,436 | 2016-09-16 | ||
| PCT/US2017/028529 WO2017184819A1 (en) | 2016-04-22 | 2017-04-20 | Nalmefene, naltrexone or derivatives thereof for use in treating (non)-alcoholic steatohepatitis or non-alcoholic fatty liver disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2717677C1 true RU2717677C1 (ru) | 2020-03-25 |
Family
ID=58668969
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2018136387A RU2717677C1 (ru) | 2016-04-22 | 2017-04-20 | Налмефен, налтрексон или их производные для применения в лечении (не)алкогольного стеатогепатита или неалкогольной жировой болезни печени |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US10045977B2 (enExample) |
| EP (1) | EP3445363A1 (enExample) |
| JP (1) | JP2019514872A (enExample) |
| KR (1) | KR20180129909A (enExample) |
| CN (2) | CN117137917A (enExample) |
| AU (1) | AU2017253228B2 (enExample) |
| BR (1) | BR112018071705A2 (enExample) |
| CA (1) | CA3021788C (enExample) |
| RU (1) | RU2717677C1 (enExample) |
| WO (1) | WO2017184819A1 (enExample) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9719068B2 (en) | 2010-05-06 | 2017-08-01 | Children's Hospital Medical Center | Methods and systems for converting precursor cells into intestinal tissues through directed differentiation |
| SG10201801654RA (en) | 2014-05-28 | 2018-04-27 | Childrens Hospital Med Ct | Methods and systems for converting precursor cells into gastric tissues through directed differentiation |
| AU2015331848B2 (en) | 2014-10-17 | 2022-03-03 | Children's Hospital Medical Center, D/B/A Cincinnati Children's Hospital Medical Center | In vivo model of human small intestine using pluripotent stem cells and methods of making and using same |
| CN109415685B (zh) | 2016-05-05 | 2023-07-04 | 儿童医院医疗中心 | 用于体外制造胃底组织的方法和与其相关的组合物 |
| US20190247373A1 (en) * | 2016-07-14 | 2019-08-15 | Children's Hospital Medical Center | Methods for treating fibrosis |
| EP4553082A3 (en) | 2016-11-04 | 2025-08-20 | Children's Hospital Medical Center | Liver organoid compositions and methods of making and using same |
| EP3548507A4 (en) | 2016-12-05 | 2020-07-15 | Children's Hospital Medical Center | COLON ORGANOIDS AND PROCESSES FOR THE PREPARATION AND USE THEREOF |
| JP7248586B2 (ja) | 2017-04-14 | 2023-03-29 | チルドレンズ ホスピタル メディカル センター | 複数ドナー幹細胞組成物およびそれを作製する方法 |
| EP3694603B1 (en) | 2017-10-10 | 2026-04-08 | Children's Hospital Medical Center | Esophageal tissue and/or organoid compositions and methods of making same |
| EP3727394A4 (en) | 2017-12-21 | 2021-09-08 | Children's Hospital Medical Center | DIGITALIZED HUMAN ORGANOIDS AND METHOD OF USING THEREOF |
| EP4678727A3 (en) | 2018-07-26 | 2026-03-11 | Children's Hospital Medical Center | Hepato-biliary-pancreatic tissues and methods of making same |
| CA3112026A1 (en) | 2018-09-12 | 2020-03-19 | Children's Hospital Medical Center | Organoid compositions for the production of hematopoietic stem cells and derivatives thereof |
| US12600943B2 (en) | 2019-02-01 | 2026-04-14 | The University Of Hong Kong | Innervated organoid compositions and methods of making same |
| US12497597B2 (en) | 2019-05-31 | 2025-12-16 | Children's Hospital Medical Center | Methods of generating and expanding hematopoietic stem cells |
| AU2020283048A1 (en) | 2019-05-31 | 2021-12-23 | Children's Hospital Medical Center | Shaped organoid compositions and methods of making same |
| EP4406534A4 (en) | 2021-11-18 | 2025-08-27 | Inventage Lab Inc | EXTENDED-RELEASE INJECTABLE COMPOSITION CONTAINING NALTREXONE AND PROCESS FOR ITS PREPARATION |
| KR20230073128A (ko) | 2021-11-18 | 2023-05-25 | (주)인벤티지랩 | 날트렉손을 포함하는 서방성 주사용 조성물 및 이의 제조 방법 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2090190C1 (ru) * | 1990-06-04 | 1997-09-20 | Алко Лтд, Орион-Ихтюмя Ой | Способ лечения алкоголизма |
| US20090169508A1 (en) * | 2003-05-16 | 2009-07-02 | Jenkin Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| CN102048733A (zh) * | 2010-12-23 | 2011-05-11 | 武汉同源药业有限公司 | 盐酸纳美芬的医药用途 |
| RU2561871C2 (ru) * | 2010-03-31 | 2015-09-10 | Ак Кимя Итхалат-Ихрацат Ве Санайии А.С. | Антагонист опиоидных рецепторов (налтрексон) для использования в терапии герпесного опоясывающего лишая |
| US20150335638A1 (en) * | 2009-07-16 | 2015-11-26 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2486157C (en) | 2002-05-17 | 2013-04-16 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US7923454B2 (en) * | 2002-05-17 | 2011-04-12 | Jenken Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| UA114360C2 (uk) * | 2013-04-22 | 2017-05-25 | Каділа Хелткере Лімітед | Спосіб лікування та/або зменшення інтенсивності неалкогольної жирової хвороби печінки (нжхп) |
| WO2017141104A2 (en) * | 2016-02-18 | 2017-08-24 | Immune Therapeutics, Inc. | Method for inducing a sustained immune response |
-
2017
- 2017-04-20 CN CN202311054107.XA patent/CN117137917A/zh active Pending
- 2017-04-20 EP EP17721252.9A patent/EP3445363A1/en not_active Ceased
- 2017-04-20 CN CN201780024846.0A patent/CN109069503A/zh active Pending
- 2017-04-20 KR KR1020187031996A patent/KR20180129909A/ko not_active Ceased
- 2017-04-20 US US15/492,198 patent/US10045977B2/en active Active
- 2017-04-20 JP JP2018554716A patent/JP2019514872A/ja active Pending
- 2017-04-20 RU RU2018136387A patent/RU2717677C1/ru active
- 2017-04-20 AU AU2017253228A patent/AU2017253228B2/en active Active
- 2017-04-20 WO PCT/US2017/028529 patent/WO2017184819A1/en not_active Ceased
- 2017-04-20 BR BR112018071705-3A patent/BR112018071705A2/pt not_active IP Right Cessation
- 2017-04-20 CA CA3021788A patent/CA3021788C/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2090190C1 (ru) * | 1990-06-04 | 1997-09-20 | Алко Лтд, Орион-Ихтюмя Ой | Способ лечения алкоголизма |
| US20090169508A1 (en) * | 2003-05-16 | 2009-07-02 | Jenkin Biosciences, Inc. | Opioid and opioid-like compounds and uses thereof |
| US20150335638A1 (en) * | 2009-07-16 | 2015-11-26 | Mallinckrodt Llc | (+)-morphinans as antagonists of toll-like receptor 9 and therapeutic uses thereof |
| RU2561871C2 (ru) * | 2010-03-31 | 2015-09-10 | Ак Кимя Итхалат-Ихрацат Ве Санайии А.С. | Антагонист опиоидных рецепторов (налтрексон) для использования в терапии герпесного опоясывающего лишая |
| CN102048733A (zh) * | 2010-12-23 | 2011-05-11 | 武汉同源药业有限公司 | 盐酸纳美芬的医药用途 |
Non-Patent Citations (1)
| Title |
|---|
| A. MOSLEHI et al. ACTA PHYSIOLOGICA HUNGARICA, vol.101. no.3, 2014, pp. 341-352. GIOVANNI ADDOLORATO et al. CNS DRUGS, vol.27, no.4, 2013, pp. 287-299. * |
Also Published As
| Publication number | Publication date |
|---|---|
| AU2017253228A8 (en) | 2019-01-17 |
| CN117137917A (zh) | 2023-12-01 |
| US10045977B2 (en) | 2018-08-14 |
| CA3021788A1 (en) | 2017-10-26 |
| CN109069503A (zh) | 2018-12-21 |
| KR20180129909A (ko) | 2018-12-05 |
| JP2019514872A (ja) | 2019-06-06 |
| US20170304294A1 (en) | 2017-10-26 |
| BR112018071705A2 (pt) | 2019-02-19 |
| AU2017253228A1 (en) | 2018-09-27 |
| AU2017253228B2 (en) | 2020-04-09 |
| WO2017184819A1 (en) | 2017-10-26 |
| CA3021788C (en) | 2021-08-03 |
| EP3445363A1 (en) | 2019-02-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2717677C1 (ru) | Налмефен, налтрексон или их производные для применения в лечении (не)алкогольного стеатогепатита или неалкогольной жировой болезни печени | |
| JP2019514872A5 (enExample) | ||
| CN105250335B (zh) | 治疗葡萄糖代谢紊乱的方法 | |
| KR100877600B1 (ko) | 메타독신 및 마늘유를 유효성분으로 함유하는 알코올성지방간 및 지방간성 간염의 예방 및 치료용 약학 조성물 | |
| CN117919232B (zh) | 吲哚丙酸在治疗肝硬化以及免疫性肝损伤的应用 | |
| Hsiao et al. | Pharmacokinetics and tissue depletion of doxycycline administered at high dosage to broiler chickens via the drinking water | |
| WO2016195355A1 (ko) | 필버톤의 신규한 용도 | |
| US11925610B2 (en) | Means to facilitate food intake and food retention | |
| JP6157928B2 (ja) | 肝臓への脂肪蓄積抑制剤 | |
| JP7184805B2 (ja) | 肥満症の予防のためのベタイン | |
| EP3923956B1 (en) | Cnidimoside a for use in the treatment of urinary conditions | |
| US20180318290A1 (en) | Use of nalmefene in non-alcoholic steatohepatitis | |
| JP6859562B1 (ja) | 脂肪肝改善用組成物 | |
| TW201813646A (zh) | 納美芬(nalmefene)在非酒精性脂肪肝炎(nash)的應用 | |
| KR20190130241A (ko) | 크로몰린 또는 이의 약학적으로 허용가능한 염을 유효성분으로 함유하는 지방간의 예방 또는 치료용 약학적 조성물 | |
| CN112641779B (zh) | Gw441756在制备预防和/或治疗脂肪肝药物中的应用 | |
| KR20260033973A (ko) | 오에노테인 b를 포함하는 대사이상 간 질환의 예방 또는 치료용 조성물 | |
| KR101541016B1 (ko) | 피노카베올의 신규한 용도 | |
| WO2015199097A1 (ja) | Ｕｃｐ－１発現促進剤 | |
| KR20210020788A (ko) | 하이드로퀴논 유도체, 및 오베티콜릭산을 포함하는 비알콜성 지방간염의 예방 또는 치료용 약학조성물 | |
| Rameshbhai | Evaluation of ethanolic leaves extract of holoptelea integrifolia for antidiabeticactivity in rats | |
| CHRONIC | DISSERTATION TITLED “BETAINE THERAPY AND ITS INFLUENCE ON OUTCOME OF ACUTE ON CHRONIC ALCOHOLIC LIVER DISEASE” |