ES2962302T3 - Tratamiento de la colestasis intrahepática y hepatopatías relacionadas - Google Patents
Tratamiento de la colestasis intrahepática y hepatopatías relacionadas Download PDFInfo
- Publication number
- ES2962302T3 ES2962302T3 ES16812728T ES16812728T ES2962302T3 ES 2962302 T3 ES2962302 T3 ES 2962302T3 ES 16812728 T ES16812728 T ES 16812728T ES 16812728 T ES16812728 T ES 16812728T ES 2962302 T3 ES2962302 T3 ES 2962302T3
- Authority
- ES
- Spain
- Prior art keywords
- composition
- bacterial strain
- activity
- subject
- bacteroides
- 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
- 208000001024 intrahepatic cholestasis Diseases 0.000 title claims abstract description 62
- 230000007872 intrahepatic cholestasis Effects 0.000 title claims abstract description 62
- 238000011282 treatment Methods 0.000 title description 40
- 208000019423 liver disease Diseases 0.000 title description 8
- 239000003613 bile acid Substances 0.000 claims abstract description 110
- 230000001580 bacterial effect Effects 0.000 claims abstract description 105
- 239000000203 mixture Substances 0.000 claims abstract description 99
- 230000000694 effects Effects 0.000 claims abstract description 59
- 238000006345 epimerization reaction Methods 0.000 claims abstract description 27
- 238000000034 method Methods 0.000 claims abstract description 20
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims description 45
- 241000124008 Mammalia Species 0.000 claims description 28
- 241000186000 Bifidobacterium Species 0.000 claims description 26
- 208000003251 Pruritus Diseases 0.000 claims description 25
- 241000961092 Collinsella aerofaciens ATCC 25986 Species 0.000 claims description 16
- 235000013406 prebiotics Nutrition 0.000 claims description 16
- 241001608472 Bifidobacterium longum Species 0.000 claims description 14
- 241000605716 Desulfovibrio Species 0.000 claims description 14
- 229940009291 bifidobacterium longum Drugs 0.000 claims description 14
- 241000193403 Clostridium Species 0.000 claims description 13
- 241000423333 Bacteroides fragilis NCTC 9343 Species 0.000 claims description 12
- 241000606125 Bacteroides Species 0.000 claims description 11
- 241000606123 Bacteroides thetaiotaomicron Species 0.000 claims description 7
- 241000186542 Clostridium baratii Species 0.000 claims description 7
- 241000604463 Desulfovibrio piger Species 0.000 claims description 7
- 241001262170 Collinsella aerofaciens Species 0.000 claims description 6
- 101710088194 Dehydrogenase Proteins 0.000 claims description 6
- 229920001202 Inulin Polymers 0.000 claims description 6
- JYJIGFIDKWBXDU-MNNPPOADSA-N inulin Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)OC[C@]1(OC[C@]2(OC[C@]3(OC[C@]4(OC[C@]5(OC[C@]6(OC[C@]7(OC[C@]8(OC[C@]9(OC[C@]%10(OC[C@]%11(OC[C@]%12(OC[C@]%13(OC[C@]%14(OC[C@]%15(OC[C@]%16(OC[C@]%17(OC[C@]%18(OC[C@]%19(OC[C@]%20(OC[C@]%21(OC[C@]%22(OC[C@]%23(OC[C@]%24(OC[C@]%25(OC[C@]%26(OC[C@]%27(OC[C@]%28(OC[C@]%29(OC[C@]%30(OC[C@]%31(OC[C@]%32(OC[C@]%33(OC[C@]%34(OC[C@]%35(OC[C@]%36(O[C@@H]%37[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O%37)O)[C@H]([C@H](O)[C@@H](CO)O%36)O)[C@H]([C@H](O)[C@@H](CO)O%35)O)[C@H]([C@H](O)[C@@H](CO)O%34)O)[C@H]([C@H](O)[C@@H](CO)O%33)O)[C@H]([C@H](O)[C@@H](CO)O%32)O)[C@H]([C@H](O)[C@@H](CO)O%31)O)[C@H]([C@H](O)[C@@H](CO)O%30)O)[C@H]([C@H](O)[C@@H](CO)O%29)O)[C@H]([C@H](O)[C@@H](CO)O%28)O)[C@H]([C@H](O)[C@@H](CO)O%27)O)[C@H]([C@H](O)[C@@H](CO)O%26)O)[C@H]([C@H](O)[C@@H](CO)O%25)O)[C@H]([C@H](O)[C@@H](CO)O%24)O)[C@H]([C@H](O)[C@@H](CO)O%23)O)[C@H]([C@H](O)[C@@H](CO)O%22)O)[C@H]([C@H](O)[C@@H](CO)O%21)O)[C@H]([C@H](O)[C@@H](CO)O%20)O)[C@H]([C@H](O)[C@@H](CO)O%19)O)[C@H]([C@H](O)[C@@H](CO)O%18)O)[C@H]([C@H](O)[C@@H](CO)O%17)O)[C@H]([C@H](O)[C@@H](CO)O%16)O)[C@H]([C@H](O)[C@@H](CO)O%15)O)[C@H]([C@H](O)[C@@H](CO)O%14)O)[C@H]([C@H](O)[C@@H](CO)O%13)O)[C@H]([C@H](O)[C@@H](CO)O%12)O)[C@H]([C@H](O)[C@@H](CO)O%11)O)[C@H]([C@H](O)[C@@H](CO)O%10)O)[C@H]([C@H](O)[C@@H](CO)O9)O)[C@H]([C@H](O)[C@@H](CO)O8)O)[C@H]([C@H](O)[C@@H](CO)O7)O)[C@H]([C@H](O)[C@@H](CO)O6)O)[C@H]([C@H](O)[C@@H](CO)O5)O)[C@H]([C@H](O)[C@@H](CO)O4)O)[C@H]([C@H](O)[C@@H](CO)O3)O)[C@H]([C@H](O)[C@@H](CO)O2)O)[C@@H](O)[C@H](O)[C@@H](CO)O1 JYJIGFIDKWBXDU-MNNPPOADSA-N 0.000 claims description 6
- 229940029339 inulin Drugs 0.000 claims description 6
- 241000606124 Bacteroides fragilis Species 0.000 claims description 4
- 241001464956 Collinsella Species 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 abstract description 15
- 238000006460 hydrolysis reaction Methods 0.000 abstract description 15
- 241000894007 species Species 0.000 description 61
- 241000894006 Bacteria Species 0.000 description 45
- 239000006041 probiotic Substances 0.000 description 33
- 235000018291 probiotics Nutrition 0.000 description 33
- 230000000529 probiotic effect Effects 0.000 description 32
- 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 22
- 210000002966 serum Anatomy 0.000 description 22
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 22
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 19
- 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 19
- 229960001661 ursodiol Drugs 0.000 description 18
- 230000002255 enzymatic effect Effects 0.000 description 16
- 201000010099 disease Diseases 0.000 description 15
- 239000003833 bile salt Substances 0.000 description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 12
- 229940093761 bile salts Drugs 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- 229960003080 taurine Drugs 0.000 description 11
- 210000001124 body fluid Anatomy 0.000 description 10
- 239000010839 body fluid Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 210000004369 blood Anatomy 0.000 description 9
- 239000008280 blood Substances 0.000 description 9
- 210000000941 bile Anatomy 0.000 description 8
- 239000003814 drug Substances 0.000 description 8
- 230000003301 hydrolyzing effect Effects 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 210000003608 fece Anatomy 0.000 description 7
- 210000004185 liver Anatomy 0.000 description 7
- 230000035935 pregnancy Effects 0.000 description 7
- 239000004471 Glycine Substances 0.000 description 6
- 230000001605 fetal effect Effects 0.000 description 6
- 210000003754 fetus Anatomy 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- 238000007254 oxidation reaction Methods 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 208000008439 Biliary Liver Cirrhosis Diseases 0.000 description 5
- 206010008609 Cholangitis sclerosing Diseases 0.000 description 5
- 206010008635 Cholestasis Diseases 0.000 description 5
- 206010008909 Chronic Hepatitis Diseases 0.000 description 5
- 208000005176 Hepatitis C Diseases 0.000 description 5
- 206010019755 Hepatitis chronic active Diseases 0.000 description 5
- 102100021711 Ileal sodium/bile acid cotransporter Human genes 0.000 description 5
- 206010067125 Liver injury Diseases 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 108091006614 SLC10A2 Proteins 0.000 description 5
- RUDATBOHQWOJDD-BSWAIDMHSA-N chenodeoxycholic 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-BSWAIDMHSA-N 0.000 description 5
- 201000001883 cholelithiasis Diseases 0.000 description 5
- 230000007870 cholestasis Effects 0.000 description 5
- 231100000359 cholestasis Toxicity 0.000 description 5
- 201000006549 dyspepsia Diseases 0.000 description 5
- 208000001130 gallstones Diseases 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 201000000742 primary sclerosing cholangitis Diseases 0.000 description 5
- 208000010157 sclerosing cholangitis Diseases 0.000 description 5
- KPRGOTLNGIBVFL-GINZOMEDSA-N 7-ketodehydroepiandrosterone Chemical group C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3C(=O)C=C21 KPRGOTLNGIBVFL-GINZOMEDSA-N 0.000 description 4
- 102100031786 Adiponectin Human genes 0.000 description 4
- 208000033222 Biliary cirrhosis primary Diseases 0.000 description 4
- 206010055690 Foetal death Diseases 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 101000775469 Homo sapiens Adiponectin Proteins 0.000 description 4
- 208000012654 Primary biliary cholangitis Diseases 0.000 description 4
- 230000009102 absorption Effects 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 4
- 229960001091 chenodeoxycholic acid Drugs 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000007803 itching Effects 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 230000002265 prevention Effects 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 208000034702 Multiple pregnancies Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000002274 desiccant Substances 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- 230000004720 fertilization Effects 0.000 description 3
- 210000000232 gallbladder Anatomy 0.000 description 3
- 230000007407 health benefit Effects 0.000 description 3
- 231100000234 hepatic damage Toxicity 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000000968 intestinal effect Effects 0.000 description 3
- 231100001046 intrauterine death Toxicity 0.000 description 3
- SMEROWZSTRWXGI-HVATVPOCSA-N lithocholic acid Chemical compound C([C@H]1CC2)[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 SMEROWZSTRWXGI-HVATVPOCSA-N 0.000 description 3
- 230000008818 liver damage Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 239000000902 placebo Substances 0.000 description 3
- 229940068196 placebo Drugs 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 230000000707 stereoselective effect Effects 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical class OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 206010023126 Jaundice Diseases 0.000 description 2
- SMEROWZSTRWXGI-UHFFFAOYSA-N Lithocholsaeure Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 SMEROWZSTRWXGI-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000005107 Premature Birth Diseases 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- 244000052616 bacterial pathogen Species 0.000 description 2
- 239000003858 bile acid conjugate Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic 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)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 2
- 230000000112 colonic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- KXGVEGMKQFWNSR-LLQZFEROSA-N deoxycholic acid Chemical compound C([C@H]1CC2)[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)[C@@H](O)C1 KXGVEGMKQFWNSR-LLQZFEROSA-N 0.000 description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 230000010235 enterohepatic circulation Effects 0.000 description 2
- 239000003925 fat Substances 0.000 description 2
- 239000011888 foil Substances 0.000 description 2
- 235000021255 galacto-oligosaccharides Nutrition 0.000 description 2
- 150000003271 galactooligosaccharides Chemical class 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 210000003494 hepatocyte Anatomy 0.000 description 2
- 239000008176 lyophilized powder Substances 0.000 description 2
- 210000001006 meconium Anatomy 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 230000009103 reabsorption Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- DKPMWHFRUGMUKF-UHFFFAOYSA-N (3alpha,5alpha,6alpha,7alpha)-3,6,7-Trihydroxycholan-24-oic acid Natural products OC1C(O)C2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)CC2 DKPMWHFRUGMUKF-UHFFFAOYSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- DXOCDBGWDZAYRQ-UHFFFAOYSA-N (3alpha,5beta)-3-Hydroxy-7-oxocholan-24 -oic acid Natural products C1CC(O)CC2CC(=O)C3C4CCC(C(CCC(O)=O)C)C4(C)CCC3C21C DXOCDBGWDZAYRQ-UHFFFAOYSA-N 0.000 description 1
- JOYGXTIHTHBSOA-UHFFFAOYSA-N 1-(4-chlorophenyl)-3-thiophen-2-ylprop-2-en-1-one Chemical compound C1=CC(Cl)=CC=C1C(=O)C=CC1=CC=CS1 JOYGXTIHTHBSOA-UHFFFAOYSA-N 0.000 description 1
- DXOCDBGWDZAYRQ-AURDAFMXSA-N 7-oxolithocholic acid Chemical compound C1C[C@@H](O)C[C@H]2CC(=O)[C@H]3[C@@H]4CC[C@H]([C@@H](CCC(O)=O)C)[C@@]4(C)CC[C@@H]3[C@]21C DXOCDBGWDZAYRQ-AURDAFMXSA-N 0.000 description 1
- 206010070545 Bacterial translocation Diseases 0.000 description 1
- 206010004659 Biliary cirrhosis Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 208000006154 Chronic hepatitis C Diseases 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- 102000002322 Egg Proteins Human genes 0.000 description 1
- 108010000912 Egg Proteins Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001951 Fetal Death Diseases 0.000 description 1
- 208000032943 Fetal Distress Diseases 0.000 description 1
- 206010016855 Foetal distress syndrome Diseases 0.000 description 1
- 241000699694 Gerbillinae Species 0.000 description 1
- 241000282575 Gorilla Species 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 201000005085 Meconium Aspiration Syndrome Diseases 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- 241001504519 Papio ursinus Species 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 208000023146 Pre-existing disease Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 208000024799 Thyroid disease Diseases 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 231100000439 acute liver injury Toxicity 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 230000007375 bacterial translocation Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940009025 chenodeoxycholate Drugs 0.000 description 1
- 230000035606 childbirth Effects 0.000 description 1
- 229940099352 cholate Drugs 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 210000003459 common hepatic duct Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000002577 cryoprotective agent Substances 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229940009976 deoxycholate Drugs 0.000 description 1
- 229960003964 deoxycholic acid Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 102000038379 digestive enzymes Human genes 0.000 description 1
- 108091007734 digestive enzymes Proteins 0.000 description 1
- 238000005906 dihydroxylation reaction Methods 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 210000001198 duodenum Anatomy 0.000 description 1
- -1 e.g. Substances 0.000 description 1
- 210000001842 enterocyte Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 231100000479 fetal death Toxicity 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000008570 general process Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940097042 glucuronate Drugs 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 244000005709 gut microbiome Species 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 231100000753 hepatic injury Toxicity 0.000 description 1
- 208000010710 hepatitis C virus infection Diseases 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
- 210000003405 ileum Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 208000028774 intestinal disease Diseases 0.000 description 1
- 230000000366 juvenile effect Effects 0.000 description 1
- 229940039696 lactobacillus Drugs 0.000 description 1
- 230000008376 long-term health Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 210000000110 microvilli Anatomy 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 210000004681 ovum Anatomy 0.000 description 1
- 239000005022 packaging material Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000011458 pharmacological treatment Methods 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 201000011461 pre-eclampsia Diseases 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 125000002328 sterol group Chemical group 0.000 description 1
- 208000002254 stillbirth Diseases 0.000 description 1
- 231100000537 stillbirth Toxicity 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000011285 therapeutic regimen Methods 0.000 description 1
- 208000021510 thyroid gland disease Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 229940014499 ursodeoxycholate Drugs 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
- A61K35/741—Probiotics
- A61K35/744—Lactic acid bacteria, e.g. enterococci, pediococci, lactococci, streptococci or leuconostocs
- A61K35/745—Bifidobacteria
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
- A61K35/66—Microorganisms or materials therefrom
- A61K35/74—Bacteria
-
- 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
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/733—Fructosans, e.g. inulin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/04—Antipruritics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Gastroenterology & Hepatology (AREA)
- Dermatology (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562266771P | 2015-12-14 | 2015-12-14 | |
| PCT/EP2016/080941 WO2017102816A1 (en) | 2015-12-14 | 2016-12-14 | Treatment of intrahepatic cholestasis and related liver diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2962302T3 true ES2962302T3 (es) | 2024-03-18 |
Family
ID=57570064
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16812728T Active ES2962302T3 (es) | 2015-12-14 | 2016-12-14 | Tratamiento de la colestasis intrahepática y hepatopatías relacionadas |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20180369297A1 (https=) |
| EP (1) | EP3389680B1 (https=) |
| JP (2) | JP2018537484A (https=) |
| KR (1) | KR20180094950A (https=) |
| CN (1) | CN109069548A (https=) |
| AU (1) | AU2016374365B2 (https=) |
| BR (1) | BR112018012022A2 (https=) |
| CA (1) | CA3008195A1 (https=) |
| CL (1) | CL2018001548A1 (https=) |
| ES (1) | ES2962302T3 (https=) |
| IL (1) | IL259480B2 (https=) |
| MX (1) | MX2018007227A (https=) |
| RU (1) | RU2743405C2 (https=) |
| SG (1) | SG11201804255QA (https=) |
| WO (1) | WO2017102816A1 (https=) |
| ZA (1) | ZA201804660B (https=) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8906668B2 (en) | 2012-11-23 | 2014-12-09 | Seres Health, Inc. | Synergistic bacterial compositions and methods of production and use thereof |
| CA3212215A1 (en) | 2012-11-23 | 2014-05-30 | Seres Therapeutics, Inc. | Synergistic bacterial compositions and methods of production and use thereof |
| EP2967077A4 (en) | 2013-03-15 | 2016-09-14 | Seres Therapeutics Inc | NETWORK-BASED MICROBIAL COMPOSITIONS AND METHOD |
| SG10201903823QA (en) | 2014-10-31 | 2019-05-30 | Whole Biome Inc | Methods and compositions relating to microbial treatment and diagnosis of disorders |
| EP3668527A1 (en) * | 2017-08-14 | 2020-06-24 | Seres Therapeutics, Inc. | Compositions and methods for treating cholestatic disease |
| CN111372596A (zh) | 2017-08-30 | 2020-07-03 | 潘德勒姆治疗公司 | 用于治疗微生物组相关病症的方法和组合物 |
| JP2021501185A (ja) | 2017-10-30 | 2021-01-14 | セレス セラピューティクス インコーポレイテッド | 抗生物質耐性を処置するための組成物及び方法 |
| CA3106315A1 (en) | 2018-07-19 | 2020-01-23 | Pendulum Therapeutics, Inc. | Methods and compositions for microbial engraftment |
| EP3870691A4 (en) | 2018-09-13 | 2022-09-07 | Xbiome Inc. | METHODS AND COMPOSITIONS FOR TREATING GASTROINTESTINAL AND INFLAMMATORY DISORDERS |
| CN112280720B (zh) * | 2020-11-19 | 2021-07-13 | 山东龙昌动物保健品有限公司 | 一株多形拟杆菌gl-02及其与胆汁酸复配的复合菌剂与应用 |
| US20250213600A1 (en) | 2022-03-18 | 2025-07-03 | Meiji Co., Ltd. | Composition for controlling growth of bacteria in the intestinal tract and use thereof |
| GB2628547A (en) * | 2023-03-27 | 2024-10-02 | Univ Newcastle | Probiotic and postbiotic compositions, products and uses thereof |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1283225B1 (it) * | 1996-03-11 | 1998-04-16 | Renata Maria Anna Ve Cavaliere | Ceppi di batteri, composizione farmaceutica contenente uno o piu' di tali ceppi e uso dei medesimi per la prevenzione e la terapia delle |
| WO2000071138A2 (en) * | 1999-05-25 | 2000-11-30 | Gregor Reid | Oral administration of lactobacillus for the maintenance of health in women |
| AUPQ899700A0 (en) * | 2000-07-25 | 2000-08-17 | Borody, Thomas Julius | Probiotic recolonisation therapy |
| CA2642431A1 (en) * | 2006-02-15 | 2007-08-23 | Nestec S.A. | Use of bifidobacterium longum for the prevention and treatment of inflammation |
| US20120128633A1 (en) * | 2009-04-30 | 2012-05-24 | Campagnie Gervaise Donone | Use of collinsella aerofaciens for reducing bloating |
| CN102539791A (zh) * | 2012-01-09 | 2012-07-04 | 宁波天康生物科技有限公司 | 总胆汁酸的定量测定及测定试剂盒 |
| AU2014331610B2 (en) * | 2013-10-03 | 2019-11-07 | Trustees Of The University Of Pennsylvania | Compositions comprising a defined microbiome and methods of use thereof |
-
2016
- 2016-12-14 CN CN201680073160.6A patent/CN109069548A/zh active Pending
- 2016-12-14 SG SG11201804255QA patent/SG11201804255QA/en unknown
- 2016-12-14 US US15/781,595 patent/US20180369297A1/en not_active Abandoned
- 2016-12-14 KR KR1020187019268A patent/KR20180094950A/ko not_active Ceased
- 2016-12-14 ES ES16812728T patent/ES2962302T3/es active Active
- 2016-12-14 AU AU2016374365A patent/AU2016374365B2/en not_active Expired - Fee Related
- 2016-12-14 RU RU2018124487A patent/RU2743405C2/ru active
- 2016-12-14 CA CA3008195A patent/CA3008195A1/en active Pending
- 2016-12-14 WO PCT/EP2016/080941 patent/WO2017102816A1/en not_active Ceased
- 2016-12-14 IL IL259480A patent/IL259480B2/en unknown
- 2016-12-14 MX MX2018007227A patent/MX2018007227A/es unknown
- 2016-12-14 BR BR112018012022-7A patent/BR112018012022A2/pt not_active IP Right Cessation
- 2016-12-14 EP EP16812728.0A patent/EP3389680B1/en active Active
- 2016-12-14 JP JP2018530858A patent/JP2018537484A/ja active Pending
-
2018
- 2018-06-11 CL CL2018001548A patent/CL2018001548A1/es unknown
- 2018-07-12 ZA ZA2018/04660A patent/ZA201804660B/en unknown
-
2022
- 2022-07-28 JP JP2022120558A patent/JP2022166039A/ja not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| RU2018124487A (ru) | 2020-01-10 |
| EP3389680C0 (en) | 2023-10-11 |
| EP3389680A1 (en) | 2018-10-24 |
| SG11201804255QA (en) | 2018-06-28 |
| IL259480B2 (en) | 2023-09-01 |
| JP2022166039A (ja) | 2022-11-01 |
| WO2017102816A1 (en) | 2017-06-22 |
| ZA201804660B (en) | 2022-12-21 |
| CN109069548A (zh) | 2018-12-21 |
| BR112018012022A2 (pt) | 2018-12-04 |
| RU2018124487A3 (https=) | 2020-05-29 |
| JP2018537484A (ja) | 2018-12-20 |
| RU2743405C2 (ru) | 2021-02-18 |
| IL259480B1 (en) | 2023-05-01 |
| CL2018001548A1 (es) | 2018-07-20 |
| CA3008195A1 (en) | 2017-06-22 |
| US20180369297A1 (en) | 2018-12-27 |
| AU2016374365A1 (en) | 2018-07-12 |
| AU2016374365B2 (en) | 2023-04-13 |
| MX2018007227A (es) | 2018-08-01 |
| KR20180094950A (ko) | 2018-08-24 |
| EP3389680B1 (en) | 2023-10-11 |
| IL259480A (en) | 2018-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| ES2962302T3 (es) | Tratamiento de la colestasis intrahepática y hepatopatías relacionadas | |
| JP2013542195A5 (https=) | ||
| Thomsen | Subcutaneous fat necrosis of the newborn and idiopathic hypercalcemia: report of a case | |
| Mayer et al. | Management of short bowel syndrome in postoperative very low birth weight infants | |
| Passariello et al. | Efficacy of a new hypotonic oral rehydration solution containing zinc and prebiotics in the treatment of childhood acute diarrhea: a randomized controlled trial | |
| JP2023501111A (ja) | 腸管における胆汁酸プロファイルを均衡させるための合成組成物 | |
| Xinias et al. | Cornstarch thickened formula reduces oesophageal acid exposure time in infants | |
| BR112013028104A2 (pt) | composição e método para tratamento de diabetes | |
| US20160354387A1 (en) | Pharmaceutical composition based on a hepatoprotector and a prebiotic, and production and application thereof | |
| ES2958918T3 (es) | Suplemento dietético para tratar la disbiosis | |
| Singh et al. | Racecadotril: A novel antidiarrheal | |
| CN115916152A (zh) | 肠胃外营养制剂 | |
| RU2318538C1 (ru) | Фармацевтическая композиция на основе гепатопротектора и пребиотика, получение и применение | |
| WO2014076638A1 (es) | Composición antiparasitaria de amplio espectro de nitazoxanida, probióticos y prebióticos | |
| HK40002061A (en) | Treatment of intrahepatic cholestasis and related liver diseases | |
| US10398717B2 (en) | Pharmaceutical composition based on a hepatoprotector and prebiotic, and method for administrating | |
| ES2896702T3 (es) | Composición para el tratamiento del estreñimiento | |
| ES2896689T3 (es) | Composición para el tratamiento del estreñimiento | |
| Parekh et al. | The Role of Gut Microflora in Obesity-Does the Data Provide an Option for Intervention? | |
| ES2955633A1 (es) | Composición para la rehabilitación intestinal | |
| Jin et al. | Actively implementing enteral nutrition to reduce parenteral nutrition-associated liver disease | |
| US3446895A (en) | Methods for treating muscular dystrophy with a 1-methyl-delta**1-androsten-17beta-ol-3-one and digitoxin | |
| US20090209503A1 (en) | Colonic delivery therapeutic agents for inflammatory bowel disease | |
| Vaghela et al. | INTERNATIONAL JOURNAL OF RESEARCH IN PHARMACEUTICAL SCIENCES | |
| Shu et al. | Effects of Yersinia enterocolitica infection on growth of the body and internal organs in newborn colostrum-deprived piglets |