JP2022173353A - 注腸剤 - Google Patents
注腸剤 Download PDFInfo
- Publication number
- JP2022173353A JP2022173353A JP2022153076A JP2022153076A JP2022173353A JP 2022173353 A JP2022173353 A JP 2022173353A JP 2022153076 A JP2022153076 A JP 2022153076A JP 2022153076 A JP2022153076 A JP 2022153076A JP 2022173353 A JP2022173353 A JP 2022173353A
- Authority
- JP
- Japan
- Prior art keywords
- budesonide
- weeks
- enema
- ulcerative colitis
- administered
- 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.)
- Pending
Links
- 241000792859 Enema Species 0.000 title abstract description 58
- 239000007920 enema Substances 0.000 title abstract description 58
- 229940095399 enema Drugs 0.000 title abstract description 55
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 claims abstract description 72
- 229960004436 budesonide Drugs 0.000 claims abstract description 71
- 206010009900 Colitis ulcerative Diseases 0.000 claims abstract description 26
- 201000006704 Ulcerative Colitis Diseases 0.000 claims abstract description 26
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims abstract description 25
- 239000004480 active ingredient Substances 0.000 claims abstract description 14
- 208000011231 Crohn disease Diseases 0.000 claims abstract description 8
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 239000003814 drug Substances 0.000 claims description 27
- 230000035876 healing Effects 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 12
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- 208000025865 Ulcer Diseases 0.000 claims description 5
- 210000004877 mucosa Anatomy 0.000 claims description 5
- 230000004797 therapeutic response Effects 0.000 claims description 5
- 210000002429 large intestine Anatomy 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 231100000397 ulcer Toxicity 0.000 claims description 2
- 206010009887 colitis Diseases 0.000 claims 2
- 239000006260 foam Substances 0.000 abstract description 11
- 238000002360 preparation method Methods 0.000 description 37
- 229940068196 placebo Drugs 0.000 description 18
- 239000000902 placebo Substances 0.000 description 18
- 229940079593 drug Drugs 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000011156 evaluation Methods 0.000 description 8
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[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 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- 206010061218 Inflammation Diseases 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 210000004347 intestinal mucosa Anatomy 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 230000000694 effects Effects 0.000 description 6
- -1 m-gresol Chemical compound 0.000 description 6
- 229920000858 Cyclodextrin Polymers 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 239000007789 gas Substances 0.000 description 5
- 229940096976 rectal foam Drugs 0.000 description 5
- 230000002411 adverse Effects 0.000 description 4
- 239000000443 aerosol Substances 0.000 description 4
- 230000003628 erosive effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229960000890 hydrocortisone Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000004400 mucous membrane Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 101800000414 Corticotropin Proteins 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 102100027467 Pro-opiomelanocortin Human genes 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 3
- 229960000258 corticotropin Drugs 0.000 description 3
- 230000013872 defecation Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 239000003995 emulsifying agent Substances 0.000 description 3
- 238000001839 endoscopy Methods 0.000 description 3
- 229940079360 enema for constipation Drugs 0.000 description 3
- 239000012046 mixed solvent Substances 0.000 description 3
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 238000012552 review Methods 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical class [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 3
- 230000036269 ulceration Effects 0.000 description 3
- 230000002792 vascular Effects 0.000 description 3
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 239000001116 FEMA 4028 Substances 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000000654 additive Substances 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
- 210000000436 anus Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 229960004853 betadex Drugs 0.000 description 2
- 208000027503 bloody stool Diseases 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000009266 disease activity Effects 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 208000035861 hematochezia Diseases 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 210000000664 rectum Anatomy 0.000 description 2
- 210000001599 sigmoid colon Anatomy 0.000 description 2
- 150000003431 steroids Chemical group 0.000 description 2
- HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- 239000000230 xanthan gum Substances 0.000 description 2
- 229920001285 xanthan gum Polymers 0.000 description 2
- 235000010493 xanthan gum Nutrition 0.000 description 2
- 229940082509 xanthan gum Drugs 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-M 4-hydroxybenzoate Chemical compound OC1=CC=C(C([O-])=O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-M 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000002389 Pouchitis Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 150000005215 alkyl ethers Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 229940094157 budesonide enema Drugs 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229940081733 cetearyl alcohol Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 239000007979 citrate buffer Substances 0.000 description 1
- 238000012321 colectomy Methods 0.000 description 1
- 230000000112 colonic effect Effects 0.000 description 1
- 238000002052 colonoscopy Methods 0.000 description 1
- 238000009109 curative therapy Methods 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 231100000517 death Toxicity 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000003979 eosinophil Anatomy 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000002594 fluoroscopy Methods 0.000 description 1
- 239000004088 foaming agent Substances 0.000 description 1
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 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
- 239000003862 glucocorticoid Substances 0.000 description 1
- 230000002489 hematologic effect Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 238000011419 induction treatment Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 239000001282 iso-butane Substances 0.000 description 1
- OOYGSFOGFJDDHP-KMCOLRRFSA-N kanamycin A sulfate Chemical group OS(O)(=O)=O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N OOYGSFOGFJDDHP-KMCOLRRFSA-N 0.000 description 1
- 210000000265 leukocyte Anatomy 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 229940043348 myristyl alcohol Drugs 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 229940070805 p-chloro-m-cresol Drugs 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000008255 pharmaceutical foam Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 229940012831 stearyl alcohol Drugs 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/12—Aerosols; Foams
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/02—Suppositories; Bougies; Bases therefor; Ovules
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Dispersion Chemistry (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Abstract
Description
[1] ブデソニドを有効成分とし、炎症性腸疾患の治療又は再燃予防のために、1回あたり1.5~2.5mgのブデソニドを1日あたり2回、12週間投与されることを特徴とする、注腸剤。
[2] ブデソニドの投与量が1回あたり2.0mgである、前記[1]の注腸剤。
[3] 潰瘍性大腸炎又はクローン病の治療又は再燃予防のために投与される、前記[1]又は[2]の注腸剤。
[4] 泡沫状又は液状である、前記[1]~[3]のいずれかの注腸剤。
[5] 1回あたり1.5~2.5mgのブデソニドを1日あたり2回、6週間投与された時点において、治療反応が認められたが大腸粘膜治癒(内視鏡所見スコア0点)には至らなかった炎症性腸疾患の患者に対して、さらに1回あたり1.5~2.5mgのブデソニドを1日あたり2回、6週間投与される、前記[1]~[4]のいずれかの注腸剤。
[6] 前記[1]~[5]のいずれかに記載の注腸剤で1回分あたり1.5~2.5mgのブデソニドを含有する注腸剤を、14回分投与可能な注腸剤パッケージ。
[7] 前記[1]~[5]のいずれかに記載の注腸剤で1回分あたり1.5~2.5mgのブデソニドを含有する注腸剤を、14回分投与可能なように調製する、注腸剤パッケージの製造方法。
活動期潰瘍性大腸炎患者を対象に、プラセボを対照とした二重盲検比較試験によりブデソニド2mgを1日2回、6週間、直腸内投与した際の粘膜治癒率を主要評価項目としてブデソニドのプラセボに対する優越性を検証するとともに安全性を調べた。また、6週間投与にて治療反応が認められたが粘膜治癒には至らなかった患者を対象に、ブデソニド2mg1日2回を更に6週間継続投与(計12週間投与)した際の安全性及び有効性を調べた(治験番号:JapicCTI-142704)。
試験には、被験薬として、1回の噴射でブデソニド2mgを含む25mL(1.35g)の白色のクリーム状の泡沫が放出される定量噴射式の注腸用エアゾール剤(直腸泡沫剤)を用いた。当該注腸用エアゾール剤は、病変が直腸及びS状結腸に限局する活動期潰瘍性大腸炎の寛解導入治療薬として、ブデソニド2mgを1日1回の用法・用量で欧州において承認されたものである(商品名:Budenofalk 2mg/dose rectal foam、ドクターファルクファーマ社製)。
また、対照薬として、外観、重量等が被験薬と識別不能で、ブデソニドを含有しない定量噴射式注腸用エアゾール剤を用いた。
活動期の潰瘍性大腸炎患者を被験者とし、被験薬を1日2回投与する群(以下、ブデソニド投与群)及び対照薬を投与する群(以下、プラセボ群)に分けた。
被験薬又は対照薬を、1日2回(朝1回、及び夜1回)、なるべく排便後に直腸内投与した。1投与当たりの噴射回数は1回であり、投与期間は6週間とし、粘膜治癒(内視鏡所見スコアが0点)に至らなかった場合は12週間投与可能とし、評価前日の夜まで投与した。各群のブデソニド投与量は、1日2回群が4mg/日であり、プラセボ群が0mg/日であった。12週間投与した被験者はブデソニド投与群が20例、プラセボ群が18例であった。
各被験者について、投与開始前(0週目)、6週間投与時点、及び12週間投与時点において、大腸内視鏡検査を行い、MMDAIの内視鏡所見スコア(0=正常又は非活動性所見、1=軽症(発赤、血管透見像の減少)、2=中等症(著明に発赤、血管透見像の消失、脆弱、びらん)、3=重症(自然出血、潰瘍))を調べた。内視鏡所見スコアの判定は、試験実施医療機関の担当医師による評価と内視鏡中央判定委員会による評価の2つを実施した。試験実施医療機関の担当医師による評価は、試験に被験者を登録する際の判断と6週間投与時にさらに6週間投与を継続するかの判断に用いた。内視鏡中央判定委員会による評価は、有効性を評価するために用いた。表1から3に示す内視鏡所見スコアは内視鏡中央判定委員会による評価を示す。12週間投与した被験者の測定結果を表1に示す。また、プラセボ群の各被験者の6週目から12週目への内視鏡所見スコアの変化を表2に、ブデソニド投与群の各被験者の6週目から12週目への内視鏡所見スコアの変化を表3に、それぞれ示す。
Claims (7)
- ブデソニドを有効成分とし、炎症性腸疾患の治療又は再燃予防のために、1回あたり1.5~2.5mgのブデソニドを1日あたり2回、12週間投与されることを特徴とする、潰瘍性大腸炎治療剤。
- ブデソニドの投与量が1回あたり2.0mgである、請求項1に記載の潰瘍性大腸炎治療剤。
- 潰瘍性大腸炎又はクローン病の治療又は再燃予防のために投与される、請求項1又は2に記載の潰瘍性大腸炎治療剤。
- 泡沫状又は液状である、請求項1から3のいずれか一項に記載の潰瘍性大腸炎治療剤。
- 1回あたり1.5~2.5mgのブデソニドを1日あたり2回、6週間投与された時点において、治療反応が認められたが大腸粘膜治癒(内視鏡所見スコア0点)には至らなかった炎症性腸疾患の患者に対して、さらに1回あたり1.5~2.5mgのブデソニドを1日あたり2回、6週間投与される、請求項1~4のいずれか一項に記載の潰瘍性大腸炎治療剤。
- 請求項1~5のいずれか一項に記載の潰瘍性大腸炎治療剤で1回あたり1.5~2.5mgのブデソニドを含有する潰瘍性大腸炎治療剤を、14回分投与可能な潰瘍性大腸炎治療剤パッケージ。
- 請求項1~5のいずれか一項に記載の潰瘍性大腸炎治療剤で1回あたり1.5~2.5mgのブデソニドを含有する潰瘍性大腸炎治療剤を、14回分投与可能なように調製する、潰瘍性大腸炎治療剤パッケージの製造方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2016254999 | 2016-12-28 | ||
JP2016254999 | 2016-12-28 | ||
JP2017253179A JP2018108993A (ja) | 2016-12-28 | 2017-12-28 | 注腸剤 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017253179A Division JP2018108993A (ja) | 2016-12-28 | 2017-12-28 | 注腸剤 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2022173353A true JP2022173353A (ja) | 2022-11-18 |
Family
ID=61027685
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017253179A Pending JP2018108993A (ja) | 2016-12-28 | 2017-12-28 | 注腸剤 |
JP2022153076A Pending JP2022173353A (ja) | 2016-12-28 | 2022-09-26 | 注腸剤 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017253179A Pending JP2018108993A (ja) | 2016-12-28 | 2017-12-28 | 注腸剤 |
Country Status (3)
Country | Link |
---|---|
US (1) | US11464733B2 (ja) |
JP (2) | JP2018108993A (ja) |
WO (1) | WO2018122086A1 (ja) |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4446891A1 (de) | 1994-12-27 | 1996-07-04 | Falk Pharma Gmbh | Stabile wäßrige Budesonid-Lösung |
US8916546B2 (en) * | 2003-08-29 | 2014-12-23 | Therapeutic Research Llc | Materials and methods for treatment and diagnosis of disorders associated with oxidative stress |
NZ581710A (en) * | 2007-06-13 | 2012-02-24 | Jay Pravda | Materials and methods for treatment and diagnosis of disorders associated with oxidative stress |
ES2622372T3 (es) * | 2012-11-09 | 2017-07-06 | Scidose Llc | Composición de enema para tratamiento de la colitis ulcerosa que tiene estabilidad a largo plazo |
TW201505635A (zh) | 2013-05-21 | 2015-02-16 | Salix Pharmaceuticals Inc | 治療潰瘍性結腸炎之方法 |
WO2016121147A1 (ja) | 2015-01-26 | 2016-08-04 | Eaファーマ株式会社 | 注腸剤 |
-
2017
- 2017-12-21 WO PCT/EP2017/083995 patent/WO2018122086A1/en active Application Filing
- 2017-12-21 US US16/472,490 patent/US11464733B2/en active Active
- 2017-12-28 JP JP2017253179A patent/JP2018108993A/ja active Pending
-
2022
- 2022-09-26 JP JP2022153076A patent/JP2022173353A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
JP2018108993A (ja) | 2018-07-12 |
WO2018122086A1 (en) | 2018-07-05 |
US11464733B2 (en) | 2022-10-11 |
US20210128456A1 (en) | 2021-05-06 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2022173567A (ja) | 注腸剤 | |
EP0893998A1 (en) | Colonic delivery of nicotine to treat inflammatory bowel disease | |
CA2861141A1 (en) | Oromucosal liquid estradiol compositions | |
JP2008534601A5 (ja) | ||
Biancone et al. | Beclomethasone dipropionate versus mesalazine in distal ulcerative colitis: a multicenter, randomized, double-blind study | |
JP2017132791A (ja) | 組み合わせ組成物 | |
CA2841358A1 (en) | Pharmaceutical compositions for rectal administration | |
Kruis et al. | Budesonide suppositories are effective and safe for treating acute ulcerative proctitis | |
JPH10158169A (ja) | 塩化トロスピウムを含んだ医薬製剤、その調整方法および使用方法 | |
JP2019532112A5 (ja) | 結節性痒疹を治療するための抗掻痒剤 | |
JP2020504118A (ja) | 炎症性腸疾患及び腸管大腸炎を処置するのに使用するための組成物 | |
EP0630649A1 (en) | Combination of an inhibitor of inducible nitric oxide synthase (iNOS) and an antiinflammatory agent, e.g. a corticosteroid | |
JP2022173353A (ja) | 注腸剤 | |
US20140349982A1 (en) | Methods of treating ulcerative colitis | |
US7705011B2 (en) | Agent for treatment and prevention of endometriosos and uterine adenomyosis | |
JP7331149B2 (ja) | 直腸および局所投与のためのゲル | |
US20150132284A1 (en) | Method of treating ulcerative colitis | |
CN105560248A (zh) | 一种治疗真菌感染的药物组合物及其制备方法和应用 | |
CN112438981A (zh) | 羟基积雪草酸制备预防或治疗溃疡性结肠炎药物中的应用 | |
US20230057930A1 (en) | Compositions for alleviating the symptoms of low anterior resection syndrome by topical administration to the neorectum | |
WO2015073846A1 (en) | Method of treating ulcerative colitis | |
US20140349983A1 (en) | Method for treating ulcerative colitis | |
Trimpi et al. | Chronic ulcerative colitis: topical treatment with methylprednisolone acetate | |
JPH05117141A (ja) | 副腎エキス含有消炎鎮痛ゲル剤 | |
Choulis | Miscellaneous drugs, materials, and medical devices |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220926 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230905 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20231205 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20240205 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20240507 |