KR20210011693A - Composition for preventing and treating inflammatory bowel disease comprising rifaximin and dioctahedral smectite - Google Patents
Composition for preventing and treating inflammatory bowel disease comprising rifaximin and dioctahedral smectite Download PDFInfo
- Publication number
- KR20210011693A KR20210011693A KR1020190088899A KR20190088899A KR20210011693A KR 20210011693 A KR20210011693 A KR 20210011693A KR 1020190088899 A KR1020190088899 A KR 1020190088899A KR 20190088899 A KR20190088899 A KR 20190088899A KR 20210011693 A KR20210011693 A KR 20210011693A
- Authority
- KR
- South Korea
- Prior art keywords
- rifaximin
- inflammatory bowel
- composition
- bowel disease
- dioctahedral smectite
- Prior art date
Links
- 208000022559 Inflammatory bowel disease Diseases 0.000 title claims abstract description 49
- NZCRJKRKKOLAOJ-XRCRFVBUSA-N rifaximin Chemical compound OC1=C(C(O)=C2C)C3=C4N=C5C=C(C)C=CN5C4=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O NZCRJKRKKOLAOJ-XRCRFVBUSA-N 0.000 title claims abstract description 42
- 229960003040 rifaximin Drugs 0.000 title claims abstract description 42
- 229910021647 smectite Inorganic materials 0.000 title claims abstract description 37
- 239000000203 mixture Substances 0.000 title claims description 32
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims description 16
- 235000013305 food Nutrition 0.000 claims description 12
- 208000011231 Crohn disease Diseases 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 7
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 6
- 208000004232 Enteritis Diseases 0.000 claims description 6
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 6
- 230000000968 intestinal effect Effects 0.000 claims description 5
- 230000002441 reversible effect Effects 0.000 claims description 5
- 208000007784 diverticulitis Diseases 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 206010001986 Amoebic dysentery Diseases 0.000 claims description 3
- 208000009137 Behcet syndrome Diseases 0.000 claims description 3
- 208000027138 indeterminate colitis Diseases 0.000 claims description 3
- 208000011140 intestinal infectious disease Diseases 0.000 claims description 3
- 230000003612 virological effect Effects 0.000 claims description 3
- 201000008827 tuberculosis Diseases 0.000 claims description 2
- 230000000694 effects Effects 0.000 description 22
- 238000012360 testing method Methods 0.000 description 16
- 239000003814 drug Substances 0.000 description 12
- 230000001225 therapeutic effect Effects 0.000 description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 201000010099 disease Diseases 0.000 description 9
- 150000003431 steroids Chemical class 0.000 description 9
- 229940079593 drug Drugs 0.000 description 8
- 230000036541 health Effects 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 235000013376 functional food Nutrition 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 206010012735 Diarrhoea Diseases 0.000 description 6
- 208000032843 Hemorrhage Diseases 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- 208000034158 bleeding Diseases 0.000 description 6
- 230000000740 bleeding effect Effects 0.000 description 6
- 230000037396 body weight Effects 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 206010038063 Rectal haemorrhage Diseases 0.000 description 4
- 235000013361 beverage Nutrition 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 208000004998 Abdominal Pain Diseases 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 210000000436 anus Anatomy 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 230000006698 induction Effects 0.000 description 3
- 230000003902 lesion Effects 0.000 description 3
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 3
- 229960004963 mesalazine Drugs 0.000 description 3
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 3
- 229960005205 prednisolone Drugs 0.000 description 3
- -1 sulfasalazine) Chemical class 0.000 description 3
- SJHPCNCNNSSLPL-CSKARUKUSA-N (4e)-4-(ethoxymethylidene)-2-phenyl-1,3-oxazol-5-one Chemical compound O1C(=O)C(=C/OCC)\N=C1C1=CC=CC=C1 SJHPCNCNNSSLPL-CSKARUKUSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 241000699666 Mus <mouse, genus> Species 0.000 description 2
- 206010037660 Pyrexia Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 208000025865 Ulcer Diseases 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000003115 biocidal effect Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 235000014633 carbohydrates Nutrition 0.000 description 2
- 235000019219 chocolate Nutrition 0.000 description 2
- 208000037976 chronic inflammation Diseases 0.000 description 2
- 230000006020 chronic inflammation Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 230000013872 defecation Effects 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 230000001976 improved effect Effects 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 208000028774 intestinal disease Diseases 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 238000010172 mouse model Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 235000010356 sorbitol Nutrition 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 235000013343 vitamin Nutrition 0.000 description 2
- 239000011782 vitamin Substances 0.000 description 2
- 229940088594 vitamin Drugs 0.000 description 2
- 229930003231 vitamin Natural products 0.000 description 2
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 2
- 229960001600 xylazine Drugs 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- 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 1
- OWEGMIWEEQEYGQ-UHFFFAOYSA-N 100676-05-9 Natural products OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OC2C(OC(O)C(O)C2O)CO)O1 OWEGMIWEEQEYGQ-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000006491 Acacia senegal Nutrition 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 201000010000 Agranulocytosis Diseases 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
- 239000005995 Aluminium silicate Substances 0.000 description 1
- PTHCMJGKKRQCBF-UHFFFAOYSA-N Cellulose, microcrystalline Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC)C(CO)O1 PTHCMJGKKRQCBF-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000000151 Colon Diverticulum Diseases 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 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
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012741 Diarrhoea haemorrhagic Diseases 0.000 description 1
- 239000004321 EU approved sweetener Substances 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 206010017964 Gastrointestinal infection Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108090001007 Interleukin-8 Proteins 0.000 description 1
- UETNIIAIRMUTSM-UHFFFAOYSA-N Jacareubin Natural products CC1(C)OC2=CC3Oc4c(O)c(O)ccc4C(=O)C3C(=C2C=C1)O UETNIIAIRMUTSM-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000007466 Male Infertility Diseases 0.000 description 1
- GUBGYTABKSRVRQ-PICCSMPSSA-N Maltose Natural products O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-PICCSMPSSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229930189077 Rifamycin Natural products 0.000 description 1
- 206010039807 Secondary adrenocortical insufficiency Diseases 0.000 description 1
- 208000019802 Sexually transmitted disease Diseases 0.000 description 1
- 206010071061 Small intestinal bacterial overgrowth Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- GUBGYTABKSRVRQ-QUYVBRFLSA-N beta-maltose Chemical compound OC[C@H]1O[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@@H]1O GUBGYTABKSRVRQ-QUYVBRFLSA-N 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000012241 calcium silicate Nutrition 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000014171 carbonated beverage Nutrition 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000013351 cheese Nutrition 0.000 description 1
- 208000019902 chronic diarrheal disease Diseases 0.000 description 1
- 230000007665 chronic toxicity Effects 0.000 description 1
- 231100000160 chronic toxicity Toxicity 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 239000008121 dextrose Substances 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 description 1
- 230000001079 digestive effect Effects 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 235000012055 fruits and vegetables Nutrition 0.000 description 1
- 235000020510 functional beverage Nutrition 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000001295 genetical effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000003862 health status Effects 0.000 description 1
- 208000035861 hematochezia Diseases 0.000 description 1
- 208000007386 hepatic encephalopathy Diseases 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 230000036737 immune function Effects 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000015788 innate immune response Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 231100001022 leukopenia Toxicity 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000000845 maltitol Substances 0.000 description 1
- 235000010449 maltitol Nutrition 0.000 description 1
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 description 1
- 229940035436 maltitol Drugs 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- 229910052901 montmorillonite Inorganic materials 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 208000030212 nutrition disease Diseases 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- LCLHHZYHLXDRQG-ZNKJPWOQSA-N pectic acid Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)O[C@H](C(O)=O)[C@@H]1OC1[C@H](O)[C@@H](O)[C@@H](OC2[C@@H]([C@@H](O)[C@@H](O)[C@H](O2)C(O)=O)O)[C@@H](C(O)=O)O1 LCLHHZYHLXDRQG-ZNKJPWOQSA-N 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229940045354 prednisolone 2 mg Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 229960003292 rifamycin Drugs 0.000 description 1
- HJYYPODYNSCCOU-ODRIEIDWSA-N rifamycin SV Chemical compound OC1=C(C(O)=C2C)C3=C(O)C=C1NC(=O)\C(C)=C/C=C/[C@H](C)[C@H](O)[C@@H](C)[C@@H](O)[C@@H](C)[C@H](OC(C)=O)[C@H](C)[C@@H](OC)\C=C\O[C@@]1(C)OC2=C3C1=O HJYYPODYNSCCOU-ODRIEIDWSA-N 0.000 description 1
- 229940069575 rompun Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 208000023087 secondary adrenal insufficiency Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000007142 small intestinal bacterial overgrowth Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- NCEXYHBECQHGNR-QZQOTICOSA-N sulfasalazine Chemical compound C1=C(O)C(C(=O)O)=CC(\N=N\C=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-QZQOTICOSA-N 0.000 description 1
- 229960001940 sulfasalazine Drugs 0.000 description 1
- NCEXYHBECQHGNR-UHFFFAOYSA-N sulfasalazine Natural products C1=C(O)C(C(=O)O)=CC(N=NC=2C=CC(=CC=2)S(=O)(=O)NC=2N=CC=CC=2)=C1 NCEXYHBECQHGNR-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000013616 tea Nutrition 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000009423 ventilation Methods 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- QYEFBJRXKKSABU-UHFFFAOYSA-N xylazine hydrochloride Chemical compound Cl.CC1=CC=CC(C)=C1NC1=NCCCS1 QYEFBJRXKKSABU-UHFFFAOYSA-N 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/16—Inorganic salts, minerals or trace elements
- A23L33/165—Complexes or chelates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
-
- 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
- A61K9/08—Solutions
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/32—Foods, ingredients or supplements having a functional effect on health having an effect on the health of the digestive tract
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
- A23V2200/324—Foods, ingredients or supplements having a functional effect on health having an effect on the immune system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Abstract
Description
본 발명은 리팍시민(Rifaximin) 및 디옥타헤드랄 스멕타이트(dioctahedral smectite)를 포함하는, 염증성 장 질환(IBD; inflammatory bowel disease)의 예방 또는 치료용 약학적 조성물에 관한 것이다.The present invention relates to a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease (IBD), including rifaximin and dioctahedral smectite.
염증성 장 질환 (Inflammatory bowel disease, IBD)은 위장관 내에 만성적인 염증을 유발하는 질환으로, 비교적 청년층부터 발병하며 복통, 발열, 설사, 하혈 등의 증상을 수반하는 질병이다. 일반적으로 염증성 장 질환은 궤양성 대장염 (Ulcerative colitis, UC)과 크론병 (Cron's disease, CD)의 2가지 형태로 분류된다. 상기 궤양성 대장염은 주로 점막을 침범하여, 문드러짐이나 궤양을 형성하는 확산성 비특이성 염증 (diffuse nonspecific inflammation)의 일종으로서, 그 원인이 명확하게 밝혀져 있지 않으며, 혈성 설사를 비롯하여 다양한 전신 증상을 유발한다. 상기 크론병은 구강에서 항문까지 이르는 전 소화관의 점막에서 궤양, 섬유화, 협착, 병변(病變)을 비연속적으로 유발하는 육아종성 염증성 병변으로, 복통, 만성 설사, 발열, 영양장애 등의 전신 증상을 수반한다.Inflammatory bowel disease (IBD) is a disease that causes chronic inflammation in the gastrointestinal tract, and it occurs in relatively young people and is accompanied by symptoms such as abdominal pain, fever, diarrhea, and bleeding. In general, inflammatory bowel disease is classified into two types: ulcerative colitis (UC) and Crohn's disease (CD). The ulcerative colitis is a type of diffuse nonspecific inflammation that mainly invades the mucous membrane and forms pats or ulcers, the cause of which is not clearly identified, and causes various systemic symptoms including bloody diarrhea. do. The Crohn's disease is a granulomatous inflammatory lesion that causes discontinuous ulcers, fibrosis, narrowing, and lesions in the mucous membrane of the entire digestive tract from the mouth to the anus, and systemic symptoms such as abdominal pain, chronic diarrhea, fever, and nutritional disorders. Entails.
상기 염증성 장 질환의 발병원인은 아직까지 구체적으로 밝혀져 있지 않으나, 면역기능의 이상이 관여하는 것으로 알려져 있으며, 이에 관여하는 면역학적 요인으로는 선천적 면역성, 사이토카인 (Cytokine)의 생성, CD4의 활성화 등이 알려져 있다. 특히, 사이토카인이 중요한 역할을 수행하는 것으로 알려져 있으며, 특히 염증 부위에서 종양괴사인자 (Tumor nerosis cytokine; TNF-α), 인터루킨 (Interluekin; IL)-1, IL-6, IL-8 생성이 궤양성 대장염과 크론병 환자에게 현저하게 증가되는 것이 확인되었다.The cause of the inflammatory bowel disease has not been specifically identified yet, but it is known that abnormalities in immune function are involved, and immunological factors involved in this include innate immunity, production of cytokines, activation of CD4, etc. This is known. In particular, it is known that cytokines play an important role, and in particular, the production of tumor nerosis cytokine (TNF-α), interluekin (IL)-1, IL-6, and IL-8 at the site of inflammation It was found to be significantly increased in patients with sexual colitis and Crohn's disease.
이러한 염증성 장 질환을 치료하기 위하여 사용되는 약물로는 스테로이드성 면역억제제, 프로스타글란딘(prostaglandins)의 생성을 차단하는 5-아미노살리실산 (5-aminosalicylic acid; 5-ASA) 계통 약물(예, 설파살라진 등), 메살라진 등이 사용되고 있으나, 이들은 염증성 장 질환의 치료효과가 미미할 뿐만 아니라 복부허실(fullness), 두통, 발진, 간질환, 백혈구 감소증, 무과립구증, 남성 불임 등의 심각한 부작용을 유발하기 때문에, 상기와 같은 치료제의 사용이 제한되고 있다.Drugs used to treat such inflammatory bowel disease include steroidal immunosuppressants, 5-aminosalicylic acid (5-ASA) drugs that block the production of prostaglandins (e.g., sulfasalazine), Mesalazine, etc., are used, but they have insignificant therapeutic effect on inflammatory bowel disease and cause serious side effects such as fullness, headache, rash, liver disease, leukopenia, agranulocytosis, and male infertility. The use of therapeutic agents is limited.
또한, 스테로이드류의 면역억제제는 부신피질 스테로이드로서, 단기적인 효과는 인정받고 있지만, 장기적인 예후를 향상시킬 수는 없으며, 유도된 감염성 질환, 2차 부신피질 부전증, 소화성 궤양, 당뇨병, 정신장애, 스테로이드성 신장병 등과 같은 부작용의 측면에서 단지 급성인 경우에만 사용되어야 하는 한계가 있다.In addition, steroid-like immunosuppressants are adrenal cortical steroids, which are recognized for short-term effects, but cannot improve long-term prognosis, and induced infectious diseases, secondary adrenal insufficiency, peptic ulcers, diabetes, mental disorders, and steroids. In terms of side effects such as kidney disease, there is a limit that should be used only in acute cases.
현재까지 염증성 장 질환에 대해 신뢰할만한 치료요법이 부재한 것으로 평가되고 있으며, 이에 따라 효과적인 치료제의 개발이 요구되고 있다.Until now, it is evaluated that there is no reliable therapy for inflammatory bowel disease, and accordingly, the development of an effective therapeutic agent is required.
본 발명의 목적은 리팍시민 및 디옥타헤드랄 스멕타이트를 포함하는, 염증성 장 질환의 예방 또는 치료용 약학적 조성물을 제공하는 것이다. An object of the present invention is to provide a pharmaceutical composition for the prevention or treatment of inflammatory bowel disease, comprising rifaximin and dioctahedral smectite.
본 발명의 다른 목적은 리팍시민 및 디옥타헤드랄 스멕타이트를 투여하는 단계를 포함하는, 염증성 장 질환의 치료방법을 제공하는 것이다.Another object of the present invention is to provide a method for treating inflammatory bowel disease, comprising administering rifaximin and dioctahedral smectite.
본 발명의 또 다른 목적은 리팍시민 및 디옥타헤드랄 스멕타이트를 포함하는, 염증성 장 질환의 예방 또는 개선용 식품 조성물을 제공하는 것이다.Another object of the present invention is to provide a food composition for preventing or improving inflammatory bowel disease, comprising rifaximin and dioctahedral smectite.
상기와 같은 목적을 달성하기 위한 본 발명의 일 측면은 리팍시민(Rifaximin) 및 디옥타헤드랄 스멕타이트(dioctahedral smectite)를 포함하는, 염증성 장 질환(IBD; inflammatory bowel disease)의 예방 또는 치료용 약학적 조성물에 관한 것이다.One aspect of the present invention for achieving the above object is a pharmaceutical for the prevention or treatment of inflammatory bowel disease (IBD), including rifaximin and dioctahedral smectite. It relates to the composition.
본 발명에서, “리팍시민(Rifaximin)”은 반합성 리파마이신 유래의 비-전신성 항생제로서, (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S,28E)-5,6,21,23,25-펜타히드록시-27-메톡시-2,4,11,16,20,22,24,26-옥타메틸-2,7-(에톡시펜타데카-[1,11,13]트리엔이미노)벤조퓨로[4,5-e]피리도[1,2-a]-벤즈이미다-졸-1,15(2H)-디온,25-아세테이트로 명명된다. 구조는 하기 화학식 1에 나타난 바와 같다.In the present invention, "Rifaximin" is a non-systemic antibiotic derived from semi-synthetic rifamycin, (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S,28E)-5 ,6,21,23,25-pentahydroxy-27-methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7-(ethoxypentadeca-[1, 11,13]trienimino)benzofuro[4,5-e]pyrido[1,2-a]-benzimida-zol-1,15(2H)-dione,25-acetate . The structure is as shown in Formula 1 below.
[화학식 1][Formula 1]
리팍시민은 위장관 흡수가 매우 낮으나 넓은 항균 활성 스펙트럼을 보인다. 위장관의 생체 이용률은 사실상 흡수되지 않아 병원성 장내 세균에 대한 최소 저해 농도를 크게 상회하고, 대장 내 생체 이용률이 높으며 위장 내 외장 부위에 미치는 영향이 제한되어 항생제 내성과 전신 이상반응의 위험을 최소화한다. 리팍시민의 사용은 위장관 감염, 간장 뇌증, 소장 세균성 과증식(SIBO), 염증성 장 질환 및 결장 게실 질환으로 확대되었다.Rifaximin has very low gastrointestinal absorption but shows a broad spectrum of antibacterial activity. Since the bioavailability of the gastrointestinal tract is virtually not absorbed, it greatly exceeds the minimum inhibitory concentration for pathogenic intestinal bacteria, has high bioavailability in the large intestine, and has limited effects on the internal and external areas of the gastrointestinal tract, minimizing the risk of antibiotic resistance and systemic adverse reactions. The use of rifaximin has been extended to gastrointestinal infections, hepatic encephalopathy, small intestinal bacterial hyperplasia (SIBO), inflammatory bowel disease and colon diverticulum disease.
본 발명에서, “디옥타헤드랄 스멕타이트(dioctahedral smectite)”는 몬트모릴로나이트 (Montmorillonite) 계통의 천매암(Phyllite) 구조의 알루미늄 실리케이트의 한 종류이다. 이는 3층구조의 점토로서, 외부에 두 개의 실리카 4면체층과 중앙에 하나의 알루미나의 8면체층으로 되어 있다. 이 층들 사이의 간격은 1.4나노미터이다. 이러한 구조는 카올린, 아타플가이트 등의 30 배에 달하는 매우 높은 이혼교환 능력을 나타내며, 다층 구조 및 유연한 점성을 나타냄으로써 우수한 피복 능력을 가진다. 이러한 물성으로 병원성 세균, 감염성 세균, 바이러스, 설사시에 급증하는 담즙산류 및 비소화성 당류, 가스에 대한 흡착, 배설 효과가 우수하며, 점막의 정상화 및 점액의 정상 분비 작용을 할 수 있음이 알려진 바 있다. In the present invention, "dioctahedral smectite" is a type of aluminum silicate having a phyllite structure of the Montmorillonite system. This is a three-layered clay, consisting of two tetrahedral layers of silica on the outside and an octahedral layer of alumina in the center. The spacing between these layers is 1.4 nanometers. This structure exhibits a very high divorce-exchange capacity, which is 30 times that of kaolin, ataflgite, etc., and has excellent coating ability by showing a multi-layered structure and flexible viscosity. With these properties, it is known that pathogenic bacteria, infectious bacteria, viruses, and bile acids and non-digestive sugars that rapidly increase during diarrhea, have excellent adsorption and excretion effects on gas, and can normalize mucous membranes and normalize mucus secretion. have.
또한, 점막 및 피부 등에 흡수되지 않아, LD50 (P.O. Mouse) > 20g / kg 과 LD50 (P.O. Rat) > 20g / kg의 매우 낮은 정도의 급성독성을 나타낼 뿐 만성독성이 없는 안전한 물질로 알려져 있다.In addition, since it is not absorbed into mucous membranes and skin, it has a very low degree of acute toxicity of LD50 (P.O. Mouse)> 20g / kg and LD50 (P.O. Rat)> 20g / kg, and is known as a safe substance without chronic toxicity.
구체적으로, 상기 리팍시민은 전체 조성물 기준 1 내지 99 중량%; 및 상기 디옥타헤드랄 스멕타이트는 전체 조성물 기준 1 내지 99중량% 포함되는 것일 수 있다. 상기 함량 범위는 대상 환자군, 약효, 구체적인 질환의 특성, 부작용 등을 고려하여 필요에 따라 적절히 변경하여 적용할 수 있다.Specifically, the rifaximin is 1 to 99% by weight based on the total composition; And the dioctahedral smectite may be included in 1 to 99% by weight based on the total composition. The content range may be appropriately changed and applied as necessary in consideration of the target patient group, drug efficacy, specific disease characteristics, side effects, and the like.
본 발명에서, “염증성 장 질환(Inflammatory bowel disease, IBD)”은 위장관 내에 만성적인 염증을 유발하는 질환으로, 원인이 명확히 밝혀져 있지는 않으나 유전적 및 환경적 영향을 받으며, 면역학적 이상에 의해 매개되는 것으로 알려져 있다. In the present invention, “Inflammatory bowel disease (IBD)” is a disease that causes chronic inflammation in the gastrointestinal tract, and the cause is not clearly identified, but is affected by genetic and environmental effects, and is mediated by immunological abnormalities. It is known.
염증성 장 질환의 증상은 구체적인 질병에 따라 차이는 있으나, 일반적으로 복통, 하복부 불쾌감, 결장의 단축(shortening of colon), 체중감소, 출혈지수 상승(출혈) 또는 배변지수 상승(설사)의 증상을 나타낼 수 있으며, 동일한 질병이라도 병변의 범위나 위치 또는 중증도에 따라 다른 양상을 나타낼 수 있다.Symptoms of inflammatory bowel disease vary depending on the specific disease, but generally indicate symptoms of abdominal pain, lower abdominal discomfort, shortening of colon, weight loss, increased bleeding index (bleeding) or increased defecation index (diarrhea). In addition, even the same disease may exhibit different aspects depending on the extent, location, or severity of the lesion.
구체적으로, 상기 염증성 장 질환은 궤양성 대장염(ulcerative colitis), 크론병(crohn's disease), 장형 베체트(intestinal behcet's disease), 불확정 대장염(indeterminate colitis), 세균성 장염, 바이러스성 장염, 아메바성 장염, 게실염(diverticulitis) 및 결핵성 장염으로 이루어진 군에서 선택되는 하나 이상인 것일 수 있으며, 상기에 제한되는 것은 아니고 모든 장에서 발생하는 염증성 질환을 모두 포함할 수 있다.Specifically, the inflammatory bowel disease is ulcerative colitis, Crohn's disease, intestinal behcet's disease, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis, diverticulitis. It may be one or more selected from the group consisting of (diverticulitis) and tuberculosis enteritis, and is not limited to the above, and may include all inflammatory diseases occurring in all intestines.
또한 구체적으로, 상기 약학적 조성물은 리팍시민 및 디옥타헤드랄 스멕타이트가 동시, 순차적 또는 역순으로 병용 투여되는 것을 특징으로 하는 것일 수 있다. 또한 리팍시민 및 디옥타헤드랄 스멕타이트의 복합제 형태일 수 있다.In addition, specifically, the pharmaceutical composition may be characterized in that rifaximin and dioctahedral smectite are administered simultaneously, sequentially, or in reverse order. It may also be in the form of a combination of rifaximin and dioctahedral smectite.
본 발명 일 실시예에서는 옥사졸론(Oxalzolone)을 도포하여 염증성 장 질환을 유발한 마우스 모델에 있어서, 리팍시민 및 디옥타헤드랄 스멕타이트를 함께 투여한 경우 체중, 배변지수 및 출혈지수의 회복을 통해 마크로스코픽 스코어가(macroscopic score)가 현저히 개선되었는 바, 우수한 치료 효과를 나타냄을 확인하였다(도 1). In one embodiment of the present invention, in a mouse model in which inflammatory bowel disease was induced by application of oxalzolone, when rifaximin and dioctahedral smectite were administered together, the macro was used to recover body weight, defecation index, and bleeding index. As the macroscopic score was remarkably improved, it was confirmed that an excellent treatment effect was shown (FIG. 1).
특히, 기존 적용되던 치료제인 리팍시민 단독 처리 군에 비해 현저히 우수한 치료 효과를 나타내었으며, 스테로이드 제제인 프레드니솔론 수준의 치료 및 개선 효과를 나타내었다. 스테로이드 제제의 경우, 염증성 장 질환 치료에 있어 관해 유도에는 효과적이나, 관해 유지에는 효과적이지 않은 것으로 알려져 있으며, 부작용이 따름에 따라 단기간 내에 중단을 해야 하는 문제가 있다.In particular, it exhibited remarkably superior therapeutic effect compared to the group treated with rifaximin alone, the previously applied treatment, and showed treatment and improvement effects at the level of prednisolone, a steroid formulation. In the case of steroid preparations, it is known to be effective in inducing remission in the treatment of inflammatory bowel disease, but not effective in maintaining remission, and there is a problem that it must be stopped within a short period of time due to side effects.
본 발명의 리팍시민 및 디옥타헤드랄 스멕타이트의 병용투여 또는 복합제 형태의 제공은 스테로이드의 부작용 문제를 해결하고, 장기 투여가 가능함으로써 지속적인 약효 유지까지 가능하게 할 수 있는 바, 만성 질환으로 이어질 수 있는 염증성 장 질환에 대한 치료 효과를 더욱 높일 수 있다. Concomitant administration of rifaximin and dioctahedral smectite of the present invention or provision of a combination formulation solves the problem of side effects of steroids, and allows long-term administration, thereby enabling sustained drug efficacy maintenance, which may lead to chronic diseases. It can further increase the therapeutic effect for inflammatory bowel disease.
본 발명의 약학적 조성물은 투여를 위하여, 상기 본 발명의 리팍시민 및 디옥타헤드랄 스멕타이트 외에 약학적으로 허용 가능한 담체, 부형제 또는 희석제를 포함할 수 있다. 상기 담체, 부형제 및 희석제로는 락토즈, 덱스트로즈, 수크로스, 솔비톨, 만니톨, 자일리톨, 에리스리톨, 말티톨, 전분, 아카시아 고무, 알지네이트, 젤라틴, 칼슘 포스페이트, 칼슘 실리케이트, 셀룰로즈, 메틸 셀룰로즈, 미정질 셀룰로스, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 탈크, 마그네슘 스테아레이트 및 광물유를 들 수 있다.For administration, the pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier, excipient, or diluent in addition to rifaximin and dioctahedral smectite of the present invention. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methyl cellulose, microcrystalline Cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate, and mineral oils.
또한, 본 발명의 약학적 조성물은 어떠한 제형으로도 적용가능하며, 구체적으로 경구용 제형 또는 비경구형 제형으로 적용될 수 있다. 비경구형 제형으로는 주사용, 도포용, 에어로졸 등의 스프레이 형일 수 있다. 더욱 구체적으로는 주사제 형태일 수 있다. 비경구 투여를 위한 제제에는 멸균된 수용액, 비수성 용제, 현탁제, 유제, 동결건조 제제, 좌제가 포함된다. 비수성 용제, 현탁제로는 프로필렌글리콜(propylene glycol), 폴리에틸렌 글리콜, 올리브 오일과 같은 식물성 기름, 에틸올레이트와 같은 주사 가능한 에스테르 등이 사용될 수 있다. In addition, the pharmaceutical composition of the present invention can be applied in any dosage form, and specifically, can be applied in an oral dosage form or a parenteral dosage form. The parenteral formulation may be a spray type such as injection, application, or aerosol. More specifically, it may be in the form of an injection. Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized formulations, and suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate may be used.
더욱 구체적으로, 본 발명의 약학적 조성물은 액제 형태일 수 있다. 리팍시민 및 디옥타헤드랄 스멕타이트의 복합제 형태를 유지하기 위해서는 액제 형태가 유리할 수 있으나, 이에 제한되는 것은 아니며, 필요에 따라 변경될 수 있다.More specifically, the pharmaceutical composition of the present invention may be in a liquid form. In order to maintain the combined form of rifaximin and dioctahedral smectite, a liquid form may be advantageous, but is not limited thereto and may be changed as necessary.
또한, 본 발명의 약학적 조성물은 약학적으로 유효한 양으로 적용될 수 있으며, "약학적으로 유효한 양"은 의학적 치료에 적용가능한 합리적인 수혜/위험 비율로 질환을 치료하기에 충분한 양을 의미하며, 유효용량 수준은 환자의 성병, 연령, 질병의 종류, 중증도, 약물의 활성, 약물에 대한 민감도, 투여 시간, 투여 경로 및 배출 비율, 치료기간, 동시 사용되는 약물을 포함한 요소 및 기타 의학 분야에 잘 알려진 요소에 따라 결정될 수 있다. In addition, the pharmaceutical composition of the present invention may be applied in a pharmaceutically effective amount, and "pharmaceutically effective amount" means an amount sufficient to treat a disease at a reasonable benefit/risk ratio applicable to medical treatment, and is effective Dosage levels depend on the patient's sexually transmitted disease, age, type of disease, severity, activity of the drug, sensitivity to the drug, time of administration, route of administration and rate of excretion, duration of treatment, factors including concurrent drugs, and other well-known medical fields. It can be determined by factors.
나아가, 본 발명의 약학적 조성물은 또 다른 치료제와 병용하여 투여될 수 있고, 종래의 다른 치료제와 순차적으로 또는 동시에 투여될 수 있다. 또한 본 발명의 약학적 조성물은 단일 또는 다중 투여될 수 있다. 상기 요소를 모두 고려하여 부작용 없이 최소한의 양으로 최대 효과를 얻을 수 있는 양을 투여하는 것이 중요하며, 당업자에 의해 필요에 따라 용이하게 결정될 수 있다. Furthermore, the pharmaceutical composition of the present invention may be administered in combination with another therapeutic agent, and may be administered sequentially or simultaneously with other conventional therapeutic agents. In addition, the pharmaceutical composition of the present invention may be administered single or multiple. It is important to administer an amount capable of obtaining the maximum effect in a minimum amount without side effects in consideration of all of the above factors, and can be easily determined as needed by a person skilled in the art.
본 발명의 다른 측면은 상기 약학적 조성물을 포함하는 염증성 장 질환의 예방 또는 치료용 키트에 관한 것이다.Another aspect of the present invention relates to a kit for the prevention or treatment of inflammatory bowel disease comprising the pharmaceutical composition.
본 발명의 키트는 그 종류가 특별히 제한되지 않으며, 당해 기술 분야에서 통상적으로 사용되는 형태의 키트를 사용할 수 있다. 본 발명의 키트는 리팍시민 및 디옥타헤드랄 스멕타이트가 각각 개별 용기에 담긴 형태, 또는 하나 이상의 구획으로 나누어진 한 개의 용기 내에 담긴 형태로 포장되어 있을 수 있으며, 상기 리팍시민 및 디옥타헤드랄 스멕타이트는 각각 1회 투여 용량의 단위 용량 형태로 포장되어 있을 수 있으나, 이에 제한되지 않는다.The type of the kit of the present invention is not particularly limited, and a kit of a type commonly used in the art may be used. The kit of the present invention may be packaged in a form in which rifaximin and dioctahedral smectite are each contained in separate containers, or in one container divided into one or more compartments, and the rifaximin and dioctahedral smectite Each may be packaged in a unit dosage form of a single dose, but is not limited thereto.
상기 키트 내의 리팍시민 및 디옥타헤드랄 스멕타이트는 투여 대상 개체의 건강 상태 등에 따라 적절한 시기에 개별적으로 병용 투여될 수 있다. 또한, 리팍시민 및 디옥타헤드랄 스멕타이트는 동시, 순차적, 또는 역순으로 개체에게 병용 투여될 수 있다.Rifaximin and dioctahedral smectite in the kit may be separately administered in combination at an appropriate time according to the health status of the subject to be administered. In addition, rifaximin and dioctahedral smectite may be co-administered to an individual in simultaneous, sequential, or reverse order.
본 발명의 또 다른 측면은 상기 약학적 조성물을 개체에 투여하는 단계를 포함하는, 염증성 장 질환의 치료방법에 관한 것이다.Another aspect of the present invention relates to a method of treating inflammatory bowel disease, comprising administering the pharmaceutical composition to a subject.
구체적으로, 상기 투여하는 단계는 리팍시민 및 디옥타헤드랄 스멕타이트를 동시, 순차적 또는 역순으로 병용 투여되는 것을 특징으로 하는 것일 수 있다. '염증성 장 질환'은 상기 설명한 바와 같다.Specifically, the administering step may be characterized in that rifaximin and dioctahedral smectite are administered simultaneously, sequentially, or in reverse order. 'Inflammatory bowel disease' is as described above.
본 발명의 용어 "개체"는 본 발명에 따른 약학적 조성물의 투여에 의해 증상이 호전될 수 있는 염증성 장 질환을 가진 동물 또는 인간을 포함한다. 본 발명에 따른 치료용 조성물을 개체에게 투여함으로써, 염증성 장 질환을 효과적으로 예방 및 치료할 수 있다. The term "subject" of the present invention includes animals or humans with inflammatory bowel disease whose symptoms can be improved by administration of the pharmaceutical composition according to the present invention. By administering the therapeutic composition according to the present invention to an individual, inflammatory bowel disease can be effectively prevented and treated.
본 발명의 용어 "투여"는 어떠한 적절한 방법으로 인간 또는 동물에게 소정의 물질을 도입하는 것을 의미하며, 본 발명에 따른 치료용 조성물의 투여 경로는 목적 조직에 도달할 수 있는 한 어떠한 일반적인 경로를 통하여 경구 또는 비경구 투여될 수 있다. 또한, 본 발명에 따른 치료용 조성물은 유효성분이 표적 세포로 이동할 수 있는 임의의 장치에 의해 투여될 수 있다. The term "administration" of the present invention means introducing a predetermined substance to humans or animals by any suitable method, and the route of administration of the therapeutic composition according to the present invention is through any general route as long as it can reach the target tissue. It can be administered orally or parenterally. In addition, the therapeutic composition according to the present invention can be administered by any device capable of moving the active ingredient to target cells.
본 발명에 따른 약학적 조성물의 바람직한 투여량은 환자의 상태 및 체중, 질병의 정도, 약물형태, 투여경로 및 기간에 따라 다르지만, 당업자에 의해 적절하게 선택될 수 있다. The preferred dosage of the pharmaceutical composition according to the present invention varies depending on the condition and weight of the patient, the degree of the disease, the drug form, the route and duration of administration, but may be appropriately selected by those skilled in the art.
본 발명의 또 다른 측면은 리팍시민 및 디옥타헤드랄 스멕타이트를 포함하는, 염증성 장 질환의 예방 또는 개선용 식품 조성물에 관한 것이다.Another aspect of the present invention relates to a food composition for preventing or improving inflammatory bowel disease, comprising rifaximin and dioctahedral smectite.
상기 식품의 종류에는 특별한 제한은 없다. 본 발명의 조성물을 첨가할 수 있는 식품은 소세지, 육류, 빵, 초콜릿류, 스넥류, 캔디류, 과자류, 라면, 피자, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알코올 음료 및 비타민 복합제 등이 있다. 음료수로 제형화할 경우에 본 발명의 조성물 외에 첨가되는 액체 성분으로는 이에 한정되지는 않으나, 통상의 음료와 같이 여러 가지 향미제 또는 천연 탄수화물 등을 추가 성분으로서 함유할 수 있다. 상술한 천연 탄수화물은 모노사카라이드(예, 포도당, 과당 등), 디사카라이드(예, 말토오스, 수크로오스 등) 및 폴리사카라이드(예, 덱스트린, 시클로덱스트린 등과 같은 통상적인 당), 및 자일리톨, 소르비톨, 에리스리톨 등의 당 알코올일 수 있다.There is no particular limitation on the type of food. Foods to which the composition of the present invention can be added include sausage, meat, bread, chocolate, snacks, candies, confectionery, ramen, pizza, other noodles, gums, dairy products including ice cream, various soups, beverages, tea, and drinks. , Alcoholic beverages and vitamin complexes. When formulated as a beverage, the liquid component added in addition to the composition of the present invention is not limited thereto, but may contain various flavoring agents or natural carbohydrates as an additional component, such as a conventional beverage. The natural carbohydrates described above are monosaccharides (e.g., glucose, fructose, etc.), disaccharides (e.g., maltose, sucrose, etc.) and polysaccharides (e.g., common sugars such as dextrin, cyclodextrin, etc.), and xylitol, sorbitol. And sugar alcohols such as erythritol.
상기 식품의 종류는 구체적으로 건강기능식품일 수 있다. 상기 건강기능 식품은 여러 가지 영양제, 비타민, 광물(전해질), 합성 풍미제 및 천연 풍미제 등의 풍미제, 착색제 및 증진제 (치즈, 초콜릿 등), 펙트산 및 그의 염, 유기산, 보호성 콜로이드 점증제, pH 조절제, 안정화제, 보존제, 글리세린, 알코올, 탄산음료에 사용되는 탄산화제 등을 함유할 수 있다. 또한, 본 발명의 건강기능 식품은 과일 및 야채 음료의 제조를 위한 과육을 함유할 수 있다. 이러한 성분은 단독으로 또는 조합으로 사용될 수 있으며, 이러한 첨가제의 비율은 조성물 전체 중량당 0.001 내지 50 중량부의 범위에서 선택되는 것이 일반적이다.The type of food may specifically be a health functional food. The health functional foods include various nutrients, vitamins, minerals (electrolytes), flavoring agents such as synthetic flavors and natural flavoring agents, coloring agents and enhancers (cheese, chocolate, etc.), pectic acid and its salts, organic acids, protective colloidal growth It may contain an agent, a pH adjuster, a stabilizer, a preservative, glycerin, alcohol, a carbonation agent used in carbonated beverages, and the like. In addition, the health functional food of the present invention may contain pulp for the manufacture of fruit and vegetable beverages. These components may be used alone or in combination, and the proportion of these additives is generally selected from 0.001 to 50 parts by weight per total weight of the composition.
상기 건강기능식품은 식품의 생체 조절 기능을 강조한 식품으로 물리적, 생화학적, 생물공학적인 방법을 이용하여 특정 목적에 작용 및 발현하도록 부가가치를 부여한 식품이다. 이러한 건강기능 식품의 성분은 생체 방어와 신체 리듬의 조절, 질환의 방지 및 회복에 관계하는 신체 조절 기능을 생체에 대하여 충분히 발휘하도록 설계하여 가공하게 되며, 식품으로 허용 가능한 식품 보조 첨가제, 감미료 또는 기능성 원료를 함유할 수 있다. The health functional food is a food that emphasizes the biological regulation function of food, and is a food that has added value to act and express it for a specific purpose by using physical, biochemical, and bioengineering methods. Ingredients of these health functional foods are designed and processed to fully exert the body's control functions related to body defense, regulation of body rhythm, prevention and recovery of diseases to the living body, and food additives, sweeteners, or functional foods acceptable as foods. It may contain raw materials.
본 발명의 조성물을 건강기능식품(또는 건강기능 음료 첨가물)으로 사용할 경우, 상기 조성물을 그대로 첨가하거나 다른 식품 또는 식품 성분과 함께 사용하고, 통상적인 방법에 따라 적절하게 사용할 수 있다. 상기 조성물의 혼합량은 그의 사용 목적(예방, 건강 또는 개선, 치료적 처치)에 따라 적합하게 결정될 수 있다. When the composition of the present invention is used as a health functional food (or health functional beverage additive), the composition may be added as it is or used with other foods or food ingredients, and may be appropriately used according to a conventional method. The mixing amount of the composition may be appropriately determined according to the purpose of use (prevention, health or improvement, therapeutic treatment).
본 발명의 리팍시민 및 디옥타헤드랄 스멕타이트를 포함하는 약학적 조성물은 염증성 장 질환에 대하여 스테로이드 제제 수준 이상의 우수한 치료 효과를 나타내면서도 부작용 문제로 인해 관해 유지가 어려운 스테로이드와 달리 관해 유지를 위한 보다 장기적인 투여가 가능함으로써 우수한 치료 효과가 더 장기적으로 유지될 수 있도록 할 수 있다. The pharmaceutical composition comprising rifaximin and dioctahedral smectite of the present invention exhibits excellent therapeutic effects above the level of steroids for inflammatory bowel disease, but is difficult to maintain due to side effects. Since the administration is possible, an excellent therapeutic effect can be maintained for a longer period of time.
본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 상세한 설명 또는 청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.The effects of the present invention are not limited to the above effects, and should be understood to include all effects that can be deduced from the configuration of the invention described in the detailed description or claims of the present invention.
도 1은 염증성 장 질환 유발 모델에서의 Macroscopic score를 측정한 결과를 나타낸 것이다.1 shows the results of measuring Macroscopic score in an inflammatory bowel disease induction model.
이하, 본 발명을 실시예에 의해 상세히 설명한다. 단, 하기 실시예는 본 발명을 예시하는 것일 뿐, 본 발명이 하기 실시예에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail by examples. However, the following examples are only illustrative of the present invention, and the present invention is not limited by the following examples.
실험예 1. 리팍시민 및 디옥타헤드랄 스멕타이트의 복합 구성 및 투여량Experimental Example 1. Complex composition and dosage of rifaximin and dioctahedral smectite
본 발명에서 사용된 리팍시민(Rifaximin) 및 디옥타헤드랄 스멕타이트(dioctahedral smectite)의 복합 구성은 하기 표 1에 나타난 바와 같다. 리팍시민은 MSN Laboratories Private Limited, India 로부터 구입하였으며, 디옥타헤드랄 스멕타이트는 Ipsen, France로부터 구입하여 사용하였다.The composite composition of rifaximin and dioctahedral smectite used in the present invention is as shown in Table 1 below. Rifaximin was purchased from MSN Laboratories Private Limited, India, and dioctahedral smectite was purchased and used from Ipsen, France.
디옥타헤드랄 스멕타이트 75mg/kgRifaximin 50mg/kg
Dioctahedral smectite 75mg/kg
0.5 w/v% 메틸셀룰로오스(Methylcellulose) 및 0.01 v/v% Tween 80을 담체(vehicle)로 하여 시험액을 조제하였다.A test solution was prepared using 0.5 w/v% methylcellulose and 0.01 v/v% Tween 80 as carriers.
실험예 2. 염증성 장 질환(inflammatory bowel diseases, IBD) 마우스 모델 제작Experimental Example 2. Inflammatory bowel diseases (IBD) mouse model production
C57BL/6NHsd 수컷, 6주령 마우스를 온도 23±3 ℃, 상대습도 55±15 %, 환기횟수 10∼20 회/hr, 조명시간 12 시간 (오전 8 시 점등∼오후 8 시 소등) 및 조도 150∼300 Lux로 유지되는 환경에서 사육하였다. 이후, 순화기간 중 건강한 것으로 판정된 동물들의 체중을 측정하고 순위화한 체중에 따라 각 군의 평균 체중이 최대한 균일하게 분포하도록 무작위법으로 분배하고, 염증성 장 질환을 유발하였다.C57BL/6NHsd male and 6-week-old mice were subjected to temperature 23±3 ℃, relative humidity 55±15%, ventilation frequency 10-20 times/hr, lighting time 12 hours (8 am to 8 pm off) and illumination 150 to It was bred in an environment maintained at 300 Lux. Thereafter, the weights of animals determined to be healthy during the acclimatization period were measured and distributed in a random manner so that the average weight of each group was distributed as uniformly as possible according to the ranked weight, and inflammatory bowel disease was induced.
장 질환 유발 개시일 및 유발 후 1 일째에 배쪽 부위를 제모한 뒤, 100 % 에탄올로 희석한 3 % 옥사졸론(Oxalzolone)을 200 μL씩 도포하였다. 장 질환 유발 후 7 일째에 해당 동물을 조레틸50(Zoletil 50, VIRBAC, France, 5 mg/kg) 및 자일라진(xylazine, Rompun®Bayer AG, Germany)을 이용하여 마취를 실시한 후, 50 % 에탄올로 희석한 1 % 옥사졸론 용액 0.15 mL을 항문을 통해 직장 내로 투여하였다. 투여한 옥사졸론 용액이 항문으로 새어나오지 않도록 투여 후 30 초간 수직 자세를 유지하도록 하였다.After hair removal on the stomach area on the initiation of intestinal disease and the first day after induction, 200 μL of 3% Oxalzolone diluted with 100% ethanol was applied. On the 7th day after induction of intestinal disease, the animal was anesthetized using zoretil 50 (Zoletil 50, VIRBAC, France, 5 mg/kg) and xylazine (xylazine, Rompun® Bayer AG, Germany), and then 50% ethanol. 0.15 mL of a 1% oxazolone solution diluted with was administered into the rectum through the anus. The administered oxazolone solution was maintained in a vertical position for 30 seconds after administration to prevent leakage into the anus.
실험예 3. 시험군의 구성 및 시험물질의 투여Experimental Example 3. Composition of test group and administration of test substance
비교예 1 및 실시예 1 내지 3의 시험물질을 상기 제조한 염증성 장 질환 모델 동물에 투여하였다. 시험군 구성은 하기 표 2에 나타난 바와 같다. The test substances of Comparative Examples 1 and 1 to 3 were administered to the inflammatory bowel disease model animals prepared above. The test group configuration is as shown in Table 2 below.
디옥타헤드랄 스멕타이트 75mg/kgRifaximin 50mg/kg
Dioctahedral smectite 75mg/kg
상기 구성에 따라, 2회/일, 7일 동안 경구투여 하였으며, 2 종의 시험물질을 투여하는 실시예 2의 경우, 각각의 시험물질을 1일 투여량의 절반씩 2회 투여하였다. 투여량은 최근 체중 측정일에 측정한 체중을 기준으로 10 mL/kg/day로 산출하여 투여하였으며, 마우스를 경배부 피부 고정법으로 고정하고, 경구투여용 존데를 이용하여 위 내에 직접 투여하였다. 체중은 시험물질 투여 전, 이후에는 1회/일, 7일 동안 측정하였다.According to the above configuration, it was orally administered twice/day for 7 days, and in the case of Example 2 in which two test substances were administered, each test substance was administered twice, half of the daily dose. The dose was calculated and administered as 10 mL/kg/day based on the body weight measured on the latest body weight measurement day, and the mouse was fixed by the cervical skin fixation method, and administered directly into the stomach using a sonde for oral administration. Body weight was measured before administration of the test substance, once/day thereafter, for 7 days.
실험예 4. 염증성 장 질환 치료효과 확인Experimental Example 4. Inflammatory Bowel Disease Treatment Effect Confirmation
투여 및 관찰기간 동안 사망을 포함한 일반 증상의 종류, 발현일 및 증상의 정도를 1 일 1 회 관찰하고 개체 별로 기록하며, 하기 표 3에 나타난 기준(disease activity index, DAI)에 따라 스코어링(scoring)을 실시하였다. During the administration and observation period, the type of general symptoms including death, the date of onset, and the degree of symptoms are observed once a day and recorded for each individual, and scoring according to the criteria (disease activity index, DAI) shown in Table 3 below. Was carried out.
Stool typeStool form
Stool type
Bleedingbleeding
Bleeding
그 결과, 도 1에 나타난 바와 같이 종래 염증성 장 질환 치료제로 알려진 바 있는 리팍시민(실시예 3)에 비해 리팍시민 및 디옥타헤드랄 스멕타이트를 함께 투여한 경우(실시예 2) 현저히 우수한 치료 효과를 나타냄을 확인하였다. 특히, 이는 스테로이드제인 프레드니솔론(실시예 1)과 유사 수준의 이상의 효과를 나타내었으며, 일부 구간(4일 째 등)에서는 프레드니솔론 보다 더욱 우수한 효과를 나타내었다.As a result, as shown in FIG. 1, when rifaximin and dioctahedral smectite were administered together compared to rifaximin (Example 3), which has been known as a conventional inflammatory bowel disease treatment agent (Example 2), remarkably excellent therapeutic effect was obtained. It was confirmed to appear. In particular, it exhibited an effect similar to that of prednisolone (Example 1), which is a steroid, and exhibited a more excellent effect than prednisolone in some sections (
실험예 5. 통계분석Experimental Example 5. Statistical Analysis
본 시험의 결과에 대하여 모수적인 다중비교(parametric multiple comparison procedures) 혹은 비모수적인 다중비교(non-parametric multiple comparison procedures)를 사용하였다. 모수적인 다중비교의 경우, 자료의 정규성을 가정하고, 모수적 일원분산분석(One-way ANOVA)으로 검정하며, 그 결과가 유의할 경우, Dunnett's multiple comparison test를 이용하여 사후검정을 실시하여 시험군간 유의한 차이를 분석하였다.Parametric multiple comparison procedures or non-parametric multiple comparison procedures were used for the results of this test. In the case of a parametric multiple comparison, the normality of the data is assumed, and the test is performed with a parametric one-way ANOVA.If the result is significant, a post-test is performed using Dunnett's multiple comparison test to be significant between the test groups. One difference was analyzed.
비모수적인 다중비교의 경우, Kruskal-Wallis'H-test로 검정하여, 그 결과가 유의할 경우 사후분석인 Dunn's multiple comparison test를 이용하여 시험군 간 유의한 차이를 분석하였다.In the case of nonparametric multiple comparison, the test was performed with the Kruskal-Wallis'H-test, and if the result was significant, the significant difference between the test groups was analyzed using the post-mortem Dunn's multiple comparison test.
통계학적 분석은 Prism 7.04(GraphPad Software Inc., San Diego, CA, USA)을 이용하여 실시하며, p값이 0.05 미만일 경우, 통계학적으로 유의한 것으로 판정하였다.Statistical analysis was performed using Prism 7.04 (GraphPad Software Inc., San Diego, CA, USA), and a p value of less than 0.05 was determined to be statistically significant.
스테로이드는 관해 유도에는 효과적이나, 관해 유지에는 효과적이지 않은 것으로 알려져 있으며, 부작용이 따름에 따라 단기간 내에 중단을 해야 하는 문제가 있다. 본 발명에서는 리팍시민 및 디옥타헤드랄 스멕타이트를 복합제로 활용하거나, 병용투여 방법을 통해 적용함으로써 스테로이드에 의한 부작용을 최소화하면서도 염증성 장 질환에 대한 치료효과를 현저히 높일 수 있도록 하였다.Steroids are known to be effective in inducing remission, but not effective in maintaining remission, and there is a problem that it must be stopped within a short period of time due to side effects. In the present invention, by using rifaximin and dioctahedral smectite as a combination or through a combination administration method, the side effects caused by steroids are minimized, and the therapeutic effect for inflammatory bowel disease can be remarkably increased.
전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다. The above description of the present invention is for illustrative purposes only, and those of ordinary skill in the art to which the present invention pertains will be able to understand that it can be easily modified into other specific forms without changing the technical spirit or essential features of the present invention. will be. Therefore, it should be understood that the embodiments described above are illustrative in all respects and not limiting. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as being distributed may also be implemented in a combined form.
본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is indicated by the claims to be described later, and all changes or modified forms derived from the meaning and scope of the claims and the concept of equivalents thereof should be construed as being included in the scope of the present invention.
Claims (11)
상기 리팍시민은 전체 조성물 기준 1 내지 99 중량% ; 및
상기 디옥타헤드랄 스멕타이트는 전체 조성물 기준 1 내지 99중량% 포함되는 것인, 약학적 조성물.The method of claim 1,
The rifaximin is 1 to 99% by weight based on the total composition; And
The dioctahedral smectite is contained in 1 to 99% by weight based on the total composition, the pharmaceutical composition.
상기 염증성 장 질환은 궤양성 대장염(ulcerative colitis), 크론병(crohn's disease), 장형 베체트(intestinal behcet's disease), 불확정 대장염(indeterminate colitis), 세균성 장염, 바이러스성 장염, 아메바성 장염, 게실염(diverticulitis) 및 결핵성 장염으로 이루어진 군에서 선택되는 하나 이상인 것인, 약학적 조성물.The method of claim 1,
The inflammatory bowel disease is ulcerative colitis, Crohn's disease, intestinal behcet's disease, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis, diverticulitis. And one or more selected from the group consisting of tuberculous enteritis, the pharmaceutical composition.
상기 조성물은 액제 형태인 것을 특징으로 하는, 약학적 조성물.The method of claim 1,
The composition is characterized in that the liquid form, pharmaceutical composition.
상기 조성물은 리팍시민 및 디옥타헤드랄 스멕타이트가 동시, 순차적 또는 역순으로 병용 투여되는 것을 특징으로 하는, 약학적 조성물.The method of claim 1,
The composition is characterized in that rifaximin and dioctahedral smectite are administered simultaneously, sequentially or in reverse order.
상기 조성물은 리팍시민 및 디옥타헤드랄 스멕타이트의 복합제 형태인 것인, 약학적 조성물.The method of claim 1,
The composition is in the form of a combination of rifaximin and dioctahedral smectite, the pharmaceutical composition.
상기 투여하는 단계는 리팍시민 및 디옥타헤드랄 스멕타이트를 동시, 순차적 또는 역순으로 병용 투여되는 것을 특징으로 하는, 치료방법.The method of claim 8,
In the administering step, rifaximin and dioctahedral smectite are administered simultaneously, sequentially, or in reverse order.
상기 염증성 장 질환은 궤양성 대장염(ulcerative colitis), 크론병(crohn's disease), 장형 베체트(intestinal behcet's disease), 불확정 대장염(indeterminate colitis), 세균성 장염, 바이러스성 장염, 아메바성 장염, 게실염(diverticulitis) 및 결핵성 장염으로 이루어진 군에서 선택되는 하나 이상인 것인, 식품 조성물.The method of claim 10,
The inflammatory bowel disease is ulcerative colitis, Crohn's disease, intestinal behcet's disease, indeterminate colitis, bacterial enteritis, viral enteritis, amoebic enteritis, diverticulitis. And one or more selected from the group consisting of tuberculosis enteritis, food composition.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190088899A KR20210011693A (en) | 2019-07-23 | 2019-07-23 | Composition for preventing and treating inflammatory bowel disease comprising rifaximin and dioctahedral smectite |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020190088899A KR20210011693A (en) | 2019-07-23 | 2019-07-23 | Composition for preventing and treating inflammatory bowel disease comprising rifaximin and dioctahedral smectite |
Publications (1)
Publication Number | Publication Date |
---|---|
KR20210011693A true KR20210011693A (en) | 2021-02-02 |
Family
ID=74559744
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR1020190088899A KR20210011693A (en) | 2019-07-23 | 2019-07-23 | Composition for preventing and treating inflammatory bowel disease comprising rifaximin and dioctahedral smectite |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR20210011693A (en) |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20030050958A (en) | 2001-12-20 | 2003-06-25 | 송우영 | External bacteriocidal composition comprising dioctaheral smectite as effective ingredient |
KR101398648B1 (en) | 2006-03-09 | 2014-06-27 | 샐릭스 파마슈티컬스 인코포레이티드 | Rifaximin anti-rectal dysfunction preparation |
-
2019
- 2019-07-23 KR KR1020190088899A patent/KR20210011693A/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR20030050958A (en) | 2001-12-20 | 2003-06-25 | 송우영 | External bacteriocidal composition comprising dioctaheral smectite as effective ingredient |
KR101398648B1 (en) | 2006-03-09 | 2014-06-27 | 샐릭스 파마슈티컬스 인코포레이티드 | Rifaximin anti-rectal dysfunction preparation |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2002543106A (en) | Anti-nausea compositions and methods | |
Byun et al. | Curcumin ameliorates the tumor-enhancing effects of a high-protein diet in an azoxymethane-induced mouse model of colon carcinogenesis | |
KR20100045457A (en) | A method for decreasing symptoms of alcohol consumption | |
US20050201996A1 (en) | Compositions and methods for treatment of skin disorders | |
KR20210002032A (en) | Novel probiotic formulation for modulating intestinal immunity | |
CN111787925A (en) | N-acetylneuraminic acid compositions and methods of use | |
WO2006019960A1 (en) | Colostrum-based treatment for irritable bowel syndrome | |
CN101360508A (en) | Pharmaceutical composition, food or drink, or feed for intestinal disease | |
KR101501375B1 (en) | Composition for preventing or treating inflammatory bowel disease comprising metformin as an active ingredient | |
KR20210011693A (en) | Composition for preventing and treating inflammatory bowel disease comprising rifaximin and dioctahedral smectite | |
KR20210011692A (en) | Composition for preventing and treating inflammatory bowel disease comprising rifaximin and niclosamide | |
Kamerling et al. | Exogenous motilin affects postprandial proximal gastric motor function and visceral sensation | |
KR20210012164A (en) | Composition for preventing and treating inflammatory bowel disease comprising niclosamide and dioctahedral smectite | |
KR20160102669A (en) | Composition for preventing or treating of Henoch-Schonlein Purpura | |
US20030207819A1 (en) | Compositions and methods for treating inflammatory connective tissue diseases | |
CN115697366A (en) | Compositions and combinations for subjects with endometriosis | |
JP2015059103A (en) | Muscular glycogen accumulation promoter | |
KR102506461B1 (en) | A composition for improving Inflammatory bowel disease comprising Tetraselmis chuii | |
Cucchiara et al. | Role of drug therapy in the treatment of gastro-oesophageal reflux disorder in children | |
KR102467678B1 (en) | A composition for improving Inflammatory bowel disease comprising Tisochrysis lutea | |
EA008765B1 (en) | Antiinflammatory preparation | |
JP2006306897A (en) | Mozuku (edible seaweed)-originating fucoidan including agent | |
Daley | The gastrointestinal system | |
JPH05236910A (en) | Amylase-inhibiting substance | |
KR20130087174A (en) | Pharmaceutical composition comprising water extract of broccoli for preventing or treating inflammatory disease |