RU2016147198A - Лекарственные формы для пероральной доставки адсорбентов в кишечник - Google Patents
Лекарственные формы для пероральной доставки адсорбентов в кишечник Download PDFInfo
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- RU2016147198A RU2016147198A RU2016147198A RU2016147198A RU2016147198A RU 2016147198 A RU2016147198 A RU 2016147198A RU 2016147198 A RU2016147198 A RU 2016147198A RU 2016147198 A RU2016147198 A RU 2016147198A RU 2016147198 A RU2016147198 A RU 2016147198A
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- Prior art keywords
- dosage form
- cellulose
- methacrylic acid
- form according
- methyl
- Prior art date
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- 210000000936 intestine Anatomy 0.000 title claims 6
- 239000003463 adsorbent Substances 0.000 title 1
- 239000003814 drug Substances 0.000 title 1
- 229940079593 drug Drugs 0.000 title 1
- 239000002552 dosage form Substances 0.000 claims 18
- 229920000642 polymer Polymers 0.000 claims 12
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims 10
- 229920001577 copolymer Polymers 0.000 claims 7
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 6
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 claims 6
- 230000001419 dependent effect Effects 0.000 claims 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims 6
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims 5
- 239000011248 coating agent Substances 0.000 claims 5
- 238000000576 coating method Methods 0.000 claims 5
- 238000000034 method Methods 0.000 claims 5
- 239000000203 mixture Substances 0.000 claims 5
- -1 (1: 2 ratio) Polymers 0.000 claims 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims 4
- 230000003115 biocidal effect Effects 0.000 claims 4
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 claims 4
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 claims 3
- 239000001856 Ethyl cellulose Substances 0.000 claims 3
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims 3
- 239000000679 carrageenan Substances 0.000 claims 3
- 235000010418 carrageenan Nutrition 0.000 claims 3
- 229920001525 carrageenan Polymers 0.000 claims 3
- 229940113118 carrageenan Drugs 0.000 claims 3
- 210000001072 colon Anatomy 0.000 claims 3
- 235000019325 ethyl cellulose Nutrition 0.000 claims 3
- 229920001249 ethyl cellulose Polymers 0.000 claims 3
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 claims 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims 2
- 206010006326 Breath odour Diseases 0.000 claims 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 claims 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims 2
- 229920001800 Shellac Polymers 0.000 claims 2
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 claims 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims 2
- 208000020832 chronic kidney disease Diseases 0.000 claims 2
- 230000000254 damaging effect Effects 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims 2
- BXFFHSIDQOFMLE-UHFFFAOYSA-N indoxyl sulfate Chemical compound C1=CC=C2C(OS(=O)(=O)O)=CNC2=C1 BXFFHSIDQOFMLE-UHFFFAOYSA-N 0.000 claims 2
- 239000010410 layer Substances 0.000 claims 2
- 239000002207 metabolite Substances 0.000 claims 2
- WGNAKZGUSRVWRH-UHFFFAOYSA-N p-cresol sulfate Chemical compound CC1=CC=C(OS(O)(=O)=O)C=C1 WGNAKZGUSRVWRH-UHFFFAOYSA-N 0.000 claims 2
- 239000008177 pharmaceutical agent Substances 0.000 claims 2
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 claims 2
- 239000004208 shellac Substances 0.000 claims 2
- 229940113147 shellac Drugs 0.000 claims 2
- 235000013874 shellac Nutrition 0.000 claims 2
- 229920003169 water-soluble polymer Polymers 0.000 claims 2
- NVEKVXJOGMAPCY-UHFFFAOYSA-N 2-(3-hydroxypropoxycarbonyl)benzoic acid Chemical compound OCCCOC(=O)C1=CC=CC=C1C(O)=O NVEKVXJOGMAPCY-UHFFFAOYSA-N 0.000 claims 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 1
- 241000193163 Clostridioides difficile Species 0.000 claims 1
- 206010009900 Colitis ulcerative Diseases 0.000 claims 1
- 208000011231 Crohn disease Diseases 0.000 claims 1
- 229940123780 DNA topoisomerase I inhibitor Drugs 0.000 claims 1
- 206010012735 Diarrhoea Diseases 0.000 claims 1
- 206010061958 Food Intolerance Diseases 0.000 claims 1
- 102000000589 Interleukin-1 Human genes 0.000 claims 1
- 108010002352 Interleukin-1 Proteins 0.000 claims 1
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims 1
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- 102000035195 Peptidases Human genes 0.000 claims 1
- 108091005804 Peptidases Proteins 0.000 claims 1
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims 1
- 239000004365 Protease Substances 0.000 claims 1
- 239000000365 Topoisomerase I Inhibitor Substances 0.000 claims 1
- 201000006704 Ulcerative Colitis Diseases 0.000 claims 1
- ZNOZWUKQPJXOIG-XSBHQQIPSA-L [(2r,3s,4r,5r,6s)-6-[[(1r,3s,4r,5r,8s)-3,4-dihydroxy-2,6-dioxabicyclo[3.2.1]octan-8-yl]oxy]-4-[[(1r,3r,4r,5r,8s)-8-[(2s,3r,4r,5r,6r)-3,4-dihydroxy-6-(hydroxymethyl)-5-sulfonatooxyoxan-2-yl]oxy-4-hydroxy-2,6-dioxabicyclo[3.2.1]octan-3-yl]oxy]-5-hydroxy-2-( Chemical compound O[C@@H]1[C@@H](O)[C@@H](OS([O-])(=O)=O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H]2OC[C@H]1O[C@H](O[C@H]1[C@H]([C@@H](CO)O[C@@H](O[C@@H]3[C@@H]4OC[C@H]3O[C@H](O)[C@@H]4O)[C@@H]1O)OS([O-])(=O)=O)[C@@H]2O ZNOZWUKQPJXOIG-XSBHQQIPSA-L 0.000 claims 1
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 claims 1
- 229910021529 ammonia Inorganic materials 0.000 claims 1
- 230000002927 anti-mitotic effect Effects 0.000 claims 1
- 239000002246 antineoplastic agent Substances 0.000 claims 1
- 230000001580 bacterial effect Effects 0.000 claims 1
- 239000000688 bacterial toxin Substances 0.000 claims 1
- 210000004534 cecum Anatomy 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 239000001913 cellulose Substances 0.000 claims 1
- 229920002301 cellulose acetate Polymers 0.000 claims 1
- WZNRVWBKYDHTKI-UHFFFAOYSA-N cellulose, acetate 1,2,4-benzenetricarboxylate Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.OC(=O)C1=CC(C(=O)O)=CC=C1C(=O)OCC1C(OC2C(C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(COC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)O2)OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)O1 WZNRVWBKYDHTKI-UHFFFAOYSA-N 0.000 claims 1
- CFBUZOUXXHZCFB-OYOVHJISSA-N chembl511115 Chemical compound COC1=CC=C([C@@]2(CC[C@H](CC2)C(O)=O)C#N)C=C1OC1CCCC1 CFBUZOUXXHZCFB-OYOVHJISSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 229950001653 cilomilast Drugs 0.000 claims 1
- 239000011247 coating layer Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000002158 endotoxin Substances 0.000 claims 1
- 239000000147 enterotoxin Substances 0.000 claims 1
- 231100000655 enterotoxin Toxicity 0.000 claims 1
- XPNLOZNCOBKRNJ-UHFFFAOYSA-N ethyl prop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C=C.COC(=O)C(C)=C XPNLOZNCOBKRNJ-UHFFFAOYSA-N 0.000 claims 1
- 206010016766 flatulence Diseases 0.000 claims 1
- 208000007386 hepatic encephalopathy Diseases 0.000 claims 1
- 229960001340 histamine Drugs 0.000 claims 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims 1
- 210000003405 ileum Anatomy 0.000 claims 1
- 150000002475 indoles Chemical class 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 claims 1
- 229960004768 irinotecan Drugs 0.000 claims 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims 1
- 150000002617 leukotrienes Chemical class 0.000 claims 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims 1
- 229920000609 methyl cellulose Polymers 0.000 claims 1
- 239000001923 methylcellulose Substances 0.000 claims 1
- 235000010981 methylcellulose Nutrition 0.000 claims 1
- 239000002636 mycotoxin Substances 0.000 claims 1
- 229910017464 nitrogen compound Inorganic materials 0.000 claims 1
- 150000002830 nitrogen compounds Chemical class 0.000 claims 1
- 239000001301 oxygen Substances 0.000 claims 1
- 229910052760 oxygen Inorganic materials 0.000 claims 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 claims 1
- 150000002989 phenols Chemical class 0.000 claims 1
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims 1
- 150000003180 prostaglandins Chemical class 0.000 claims 1
- 239000011347 resin Substances 0.000 claims 1
- 229920005989 resin Polymers 0.000 claims 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 claims 1
- 125000005591 trimellitate group Chemical group 0.000 claims 1
- 229920002554 vinyl polymer Polymers 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
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Claims (30)
1. Лекарственная форма для пероральной доставки активированного древесного угля в кишечник, содержащая:
- сердцевину, включающую композицию, содержащую активированный древесный уголь, смешанный с каррагенаном, предпочтительно в форме таблетки, и
- слой наружного покрытия, образованного вокруг сердцевины, так что активированный древесный уголь высвобождается из формы в требуемом отделе кишечника.
2. Лекарственная форма по п. 1, где каррагенан представляет собой каппа-каррагенан.
3. Лекарственная форма по п. 1 или 2, где количество каррагенана включает от 5% и 25%, более предпочтительно, между 10 и 20% от веса композиции.
4. Лекарственная форма по п. 1, где наружное покрытие является pH-зависимым кишечнорастворимым полимером.
5. Лекарственная форма по п. 4, где pH-зависимый кишечнорастворимый полимер выбран из группы, состоящей из ацетата тримеллитата целлюлезы (CAT), ацетата фталата целлюлезы (CAP), анионных сополимеров на основе метилакрилата, метилметакрилата и метакриловой кислоты, гидроксипропилфталатметилцеллюлезы (HPMCP), ацетатсукцинатгидроксипропилметилцеллюлезы (HPMCAS), сополимеров метакриловой кислоты и этилакрилата, сополимеров метакриловой кислоты и метилакрилата, (отношение 1:1), сополимеров метакриловой кислоты и метилакрилата, (отношение 1:2), поливинилацетатфталата (PVAP) и шеллачных смол.
6. Лекарственная форма по п. 4 или 5, где полимер растворяется при pH, равном 6,0 и более.
7. Лекарственная форма по п. 6, где pH-зависимый полимер выбран из группы, состоящей из:
- шеллака,
- ацетатсукцинатгидроксиметилцеллюлезы,
- талатгидроксипропилметилцеллюлозы,
- анионных сополимеров на основе метилакрилата, метилметакрилата и метакриловой кислоты, и
- сополимера метакриловой кислоты и метилметакрилата (соотношение 1:2).
8. Лекарственная форма по п. 1, где наружное покрытие является смесью метилметакрилата и метакриловой кислоты и сополимера метакриловой кислоты и этилакрилата при отношении между 99:1 и 80:20.
9. Лекарственная форма по любому из пп. 1-5 и 7-8, где осуществлено дополнительное покрытие между сердцевиной и внешним рН-зависимым покрытием, причем упомянутое дополнительное покрытие, в частности, выбрано из группы, состоящей из
- pH-зависимых полимеров, в том числе, полимеров типа шеллака, анионных сополимеров на основе метилакрилата, метилметакрилата и метакриловой кислоты, сополимера метакриловой кислоты и этилакрилата, фталатгидроксипропил метилцеллюлезы (HPMCP), ацетатсукцинатгидроксипропилметилцеллюлезы (HPMCAS),
- pH-независимого водорастворимого полимера, такого как PVP или высокомолекулярных целлюлезных полимеров, таких как гидроксипропилметил-целлюлеза (HPMC) или гидроксипропилцеллюлеза (HPC),
- pH-независимых водорастворимых полимеров, таких как полимеры этилцеллюлезы или сополимеры этилакрилатаметилметакрилата,
- смеси pH-зависимого полимера и не растворимого в воде pH-независимого полимера, такого как этилцеллюлеза или сополимер этилакрилатметилметакрилата (NE30D).
10. Лекарственная форма по п. 9, где полимерный слой, который растворяется рН-независимым образом, и содержит по меньшей мере одно производное целлюлезы, выбранное из группы, состоящей из гидроксипропилцеллюлезы или этилцеллюлезы.
11. Лекарственная форма по п. 9, где полимерный слой, который растворяется pH-независимым образом, и составлен из 1:9 дo 9:1, предпочтительно, от 2:8 до 3:7 смеси сополимера метакриловой кислоты и сополимера этил акрилата и сополимера этил акрилата метилметакрилата.
12. Лекарственная форма по п. 1, для применения в методе устранения или уменьшения в кишечнике, в частности, в толстой кишке побочных эффектов фармацевтических агентов, вводимых для лечения заболеваний, но оказывающих повреждающее действие, когда они или их метаболиты и производные достигают нижнего отдела илеума, слепой кишки или толстой кишки.
13. Лекарственная форма по п. 12 для применения в методе устранения или уменьшения связанных с антибиотиками повреждающих эффектов антибиотических агентов, в частности, для устранения или уменьшения проявления устойчивости к антибиотикам или для устранения или уменьшения диареи.
14. Лекарственная форма по п. 13, где упомянутый антибиотик и упомянутую форму вводят одновременно оральным способом.
15. Лекарственная форма по п. 12, где упомянутый фармацевтический агент выбран в группе, включающей противоопухолевые агенты, например, ингибиторы топоизомеразы I, такие как Иринотекан, противовоспалительные соединения или ингибиторы интерлейкина-1, такого как диасцерхеин, панкреалипаза, селективный ингибитор фосфодиэстеразы 4, используемые для лечения хроничекого обструктивного заболевания легких (COPD), такие как рофумиласт или циломиласт, обладающих противовоспалительными и антимитотическими активностями, такие как колхицины, иринотекан или их метаболиты, в частности, SN-38.
16. Лекарственная форма по п. 1 для использования в методе устранения эффектов бактериальных или грибковых токсинов, таких как митотоксины, эндотоксины или энтеротоксины или образованных Clostridium difficile в кишечнике до того, как они достигают толстой кишки.
17. Лекарственная форма по п. 1 для использования в методе лечения, выбранного в группе, включающей хроническое заболевания почек, (CKD), воспалительные кишечные заболевания (IBDs), в частности язвенный колит или болезнь Крона и печеночная энцефалопатия.
18. Лекарственная форма по п. 1 для использования в методе устранения или уменьшения количества AGE, фенолов (например, п-крезилсульфата), индолов (например, индоксил сульфата), оксида азота, радикалов кислорода, простагландинов, лейкотриенов, гистамина, протеаз, матриксных металлопротеиназ или азотистыми соединениями, а именно, аммония в нижнем отделе кишечника.
19. Применение формы по пп. 1-11 для снижения метеоризма, неприятного запаха стула, неприятного запаха изо рта или непереносимости пищи, в частности, у домашних или сельскохозяйственных животных.
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| JP2010510196A (ja) * | 2006-11-17 | 2010-04-02 | ダ・ボルテラ | オイドラギット被覆を施した亜鉛／ペクチンビーズを使用する結腸送達 |
| WO2008073517A1 (en) * | 2006-12-07 | 2008-06-19 | Ehrenpreis Eli D | Treatment for intestinal gas, bloating, microscopic colitis and traveler's diarrhea using colloidal bismuth subcitrate |
| US20100036002A1 (en) * | 2006-12-26 | 2010-02-11 | Medrx Co., Ltd. | Pharmaceutical composition comprising porous dry matrix |
| DE102007009242A1 (de) | 2007-02-22 | 2008-09-18 | Evonik Röhm Gmbh | Pellets mit magensaftresistenter Wirkstoff-Matix |
| US20090148538A1 (en) * | 2007-10-12 | 2009-06-11 | Ocera Therapeutics, Inc. | Use of adsorbent carbon microspheres to treat pouchitis |
| DE102008014109A1 (de) | 2008-03-13 | 2009-09-17 | Bayer Animal Health Gmbh | Suspensionsformulierung für Kohlenstoff-Adsorbentien |
| KR20100001892A (ko) | 2008-06-27 | 2010-01-06 | 주식회사 에코비젼 | 핵입자를 함유하는 질산화 미생물의 그래뉼 및 질산화미생물의 그래뉼화 촉진방법 |
| FR2950252B1 (fr) | 2009-09-23 | 2012-01-20 | Centre Nat Rech Scient | Forme galenique capable d'adsorber de maniere specifique les molecules indesirables |
| ES2586135T3 (es) * | 2010-02-23 | 2016-10-11 | Da Volterra | Formulaciones para el suministro oral de adsorbentes en el intestino |
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2011
- 2011-02-23 ES ES11704468.5T patent/ES2586135T3/es active Active
- 2011-02-23 PT PT117044685T patent/PT2538930T/pt unknown
- 2011-02-23 KR KR1020127025014A patent/KR101820374B1/ko active IP Right Grant
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- 2011-02-23 EP EP11704468.5A patent/EP2538930B1/en active Active
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