CN105828807B - 用于在治疗肠病症中口服施用薄荷醇的释放改变的治疗系统 - Google Patents
用于在治疗肠病症中口服施用薄荷醇的释放改变的治疗系统 Download PDFInfo
- Publication number
- CN105828807B CN105828807B CN201480067078.3A CN201480067078A CN105828807B CN 105828807 B CN105828807 B CN 105828807B CN 201480067078 A CN201480067078 A CN 201480067078A CN 105828807 B CN105828807 B CN 105828807B
- Authority
- CN
- China
- Prior art keywords
- composition according
- menthol
- hydroxypropyl methylcellulose
- core
- hydroxypropylmethylcellulose
- 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.)
- Expired - Fee Related
Links
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 title claims abstract description 31
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 title claims abstract description 28
- 229940041616 menthol Drugs 0.000 title claims abstract description 28
- 208000028774 intestinal disease Diseases 0.000 title description 3
- 230000001225 therapeutic effect Effects 0.000 title description 2
- 239000011159 matrix material Substances 0.000 claims abstract description 19
- 230000002496 gastric effect Effects 0.000 claims abstract description 17
- 239000011248 coating agent Substances 0.000 claims abstract description 16
- 238000000576 coating method Methods 0.000 claims abstract description 16
- 210000001072 colon Anatomy 0.000 claims abstract description 13
- 230000003111 delayed effect Effects 0.000 claims abstract description 9
- 239000002245 particle Substances 0.000 claims abstract description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 41
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 37
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 37
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 32
- 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 claims description 32
- 239000004480 active ingredient Substances 0.000 claims description 21
- 208000002551 irritable bowel syndrome Diseases 0.000 claims description 11
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 11
- 229920001800 Shellac Polymers 0.000 claims description 9
- 239000004208 shellac Substances 0.000 claims description 9
- 229940113147 shellac Drugs 0.000 claims description 9
- 235000013874 shellac Nutrition 0.000 claims description 9
- 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 description 9
- 239000004615 ingredient Substances 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 claims description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 5
- 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 description 5
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 5
- 239000003085 diluting agent Substances 0.000 claims description 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 235000010445 lecithin Nutrition 0.000 claims description 5
- 239000000787 lecithin Substances 0.000 claims description 5
- 229940067606 lecithin Drugs 0.000 claims description 5
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 4
- 235000010443 alginic acid Nutrition 0.000 claims description 4
- 239000000783 alginic acid Substances 0.000 claims description 4
- 229920000615 alginic acid Polymers 0.000 claims description 4
- 229960001126 alginic acid Drugs 0.000 claims description 4
- 150000004781 alginic acids Chemical class 0.000 claims description 4
- 239000007884 disintegrant Substances 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 229920000642 polymer Polymers 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical group [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 235000019700 dicalcium phosphate Nutrition 0.000 claims description 3
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 claims description 3
- 239000000284 extract Substances 0.000 claims description 3
- 229920005862 polyol Polymers 0.000 claims description 3
- 150000003077 polyols Chemical class 0.000 claims description 3
- 230000002048 spasmolytic effect Effects 0.000 claims description 3
- -1 spasmolytics Substances 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 229940032147 starch Drugs 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- 239000000080 wetting agent Substances 0.000 claims description 3
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000004380 Cholic acid Substances 0.000 claims description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 2
- ZPVGIKNDGJGLCO-VGAMQAOUSA-N [(2s,3r,4s,5s,6r)-2-[(2s,3s,4s,5r)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)O[C@@]1([C@]2(CO)[C@H]([C@H](O)[C@@H](CO)O2)O)O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O ZPVGIKNDGJGLCO-VGAMQAOUSA-N 0.000 claims description 2
- 239000003242 anti bacterial agent Substances 0.000 claims description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 claims description 2
- 239000002260 anti-inflammatory agent Substances 0.000 claims description 2
- 229940088710 antibiotic agent Drugs 0.000 claims description 2
- 235000019416 cholic acid Nutrition 0.000 claims description 2
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 claims description 2
- 229960002471 cholic acid Drugs 0.000 claims description 2
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 claims description 2
- 102000038379 digestive enzymes Human genes 0.000 claims description 2
- 108091007734 digestive enzymes Proteins 0.000 claims description 2
- 239000000835 fiber Substances 0.000 claims description 2
- 239000002563 ionic surfactant Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000002736 nonionic surfactant Substances 0.000 claims description 2
- 150000003904 phospholipids Chemical class 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 2
- 235000013406 prebiotics Nutrition 0.000 claims description 2
- 239000006041 probiotic Substances 0.000 claims description 2
- 235000018291 probiotics Nutrition 0.000 claims description 2
- 229940079862 sodium lauryl sarcosinate Drugs 0.000 claims description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 2
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 2
- 239000008109 sodium starch glycolate Substances 0.000 claims description 2
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 2
- ADWNFGORSPBALY-UHFFFAOYSA-M sodium;2-[dodecyl(methyl)amino]acetate Chemical compound [Na+].CCCCCCCCCCCCN(C)CC([O-])=O ADWNFGORSPBALY-UHFFFAOYSA-M 0.000 claims description 2
- 210000002784 stomach Anatomy 0.000 claims description 2
- 230000000699 topical effect Effects 0.000 claims description 2
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims 2
- 159000000007 calcium salts Chemical class 0.000 claims 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims 2
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims 1
- 239000003086 colorant Substances 0.000 claims 1
- 159000000003 magnesium salts Chemical class 0.000 claims 1
- 229920000193 polymethacrylate Polymers 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- 230000000694 effects Effects 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 238000009472 formulation Methods 0.000 description 6
- 230000000968 intestinal effect Effects 0.000 description 6
- 150000003839 salts Chemical class 0.000 description 6
- 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 5
- 229930195725 Mannitol Natural products 0.000 description 5
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 5
- 235000019359 magnesium stearate Nutrition 0.000 description 5
- 239000000594 mannitol Substances 0.000 description 5
- 235000010355 mannitol Nutrition 0.000 description 5
- 239000001506 calcium phosphate Substances 0.000 description 4
- 229910000389 calcium phosphate Inorganic materials 0.000 description 4
- 235000011010 calcium phosphates Nutrition 0.000 description 4
- 235000010980 cellulose Nutrition 0.000 description 4
- 229920002678 cellulose Polymers 0.000 description 4
- 239000001913 cellulose Substances 0.000 description 4
- 230000000112 colonic effect Effects 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 238000007922 dissolution test Methods 0.000 description 4
- 239000007888 film coating Substances 0.000 description 4
- 238000009501 film coating Methods 0.000 description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 description 4
- 102220487426 Actin-related protein 2/3 complex subunit 3_K15M_mutation Human genes 0.000 description 3
- 244000246386 Mentha pulegium Species 0.000 description 3
- 235000016257 Mentha pulegium Nutrition 0.000 description 3
- 235000004357 Mentha x piperita Nutrition 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 235000001050 hortel pimenta Nutrition 0.000 description 3
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 3
- 235000019477 peppermint oil Nutrition 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229920003093 Methocel™ K100 LV Polymers 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 108010037150 Transient Receptor Potential Channels Proteins 0.000 description 2
- 102000011753 Transient Receptor Potential Channels Human genes 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000001174 ascending effect Effects 0.000 description 2
- 239000013060 biological fluid Substances 0.000 description 2
- 239000008139 complexing agent Substances 0.000 description 2
- 229960005168 croscarmellose Drugs 0.000 description 2
- 229960000913 crospovidone Drugs 0.000 description 2
- 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- AGBQKNBQESQNJD-UHFFFAOYSA-N lipoic acid Chemical compound OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 238000007909 melt granulation Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 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 2
- 238000005550 wet granulation Methods 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- NEBPTMCRLHKPOB-UHFFFAOYSA-N 2,2-diphenylacetonitrile Chemical compound C=1C=CC=CC=1C(C#N)C1=CC=CC=C1 NEBPTMCRLHKPOB-UHFFFAOYSA-N 0.000 description 1
- LORDFXWUHHSAQU-UHFFFAOYSA-N 3,4,5-trimethoxybenzoic acid [2-(dimethylamino)-2-phenylbutyl] ester Chemical compound C=1C=CC=CC=1C(CC)(N(C)C)COC(=O)C1=CC(OC)=C(OC)C(OC)=C1 LORDFXWUHHSAQU-UHFFFAOYSA-N 0.000 description 1
- 208000004998 Abdominal Pain Diseases 0.000 description 1
- 206010000060 Abdominal distension Diseases 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 240000002234 Allium sativum Species 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
- JEBFVOLFMLUKLF-IFPLVEIFSA-N Astaxanthin Natural products CC(=C/C=C/C(=C/C=C/C1=C(C)C(=O)C(O)CC1(C)C)/C)C=CC=C(/C)C=CC=C(/C)C=CC2=C(C)C(=O)C(O)CC2(C)C JEBFVOLFMLUKLF-IFPLVEIFSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 235000018062 Boswellia Nutrition 0.000 description 1
- 240000007551 Boswellia serrata Species 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 235000007866 Chamaemelum nobile Nutrition 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 229920000858 Cyclodextrin Polymers 0.000 description 1
- 244000019459 Cynara cardunculus Species 0.000 description 1
- 235000019106 Cynara scolymus Nutrition 0.000 description 1
- IMXSCCDUAFEIOE-UHFFFAOYSA-N D-Octopin Natural products OC(=O)C(C)NC(C(O)=O)CCCN=C(N)N IMXSCCDUAFEIOE-UHFFFAOYSA-N 0.000 description 1
- IMXSCCDUAFEIOE-RITPCOANSA-N D-octopine Chemical compound [O-]C(=O)[C@@H](C)[NH2+][C@H](C([O-])=O)CCCNC(N)=[NH2+] IMXSCCDUAFEIOE-RITPCOANSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 244000133098 Echinacea angustifolia Species 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 101000764872 Homo sapiens Transient receptor potential cation channel subfamily A member 1 Proteins 0.000 description 1
- 241000186660 Lactobacillus Species 0.000 description 1
- 102000010445 Lactoferrin Human genes 0.000 description 1
- 108010063045 Lactoferrin Proteins 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
- 244000042664 Matricaria chamomilla Species 0.000 description 1
- 235000007232 Matricaria chamomilla Nutrition 0.000 description 1
- 244000182807 Mentha suaveolens Species 0.000 description 1
- 235000002899 Mentha suaveolens Nutrition 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- 229920003096 Methocel™ K100M Polymers 0.000 description 1
- 229920003095 Methocel™ K15M Polymers 0.000 description 1
- 229920003094 Methocel™ K4M Polymers 0.000 description 1
- 208000007101 Muscle Cramp Diseases 0.000 description 1
- 244000134552 Plantago ovata Species 0.000 description 1
- 235000003421 Plantago ovata Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 229920000148 Polycarbophil calcium Polymers 0.000 description 1
- VVWYOYDLCMFIEM-UHFFFAOYSA-N Propantheline Chemical compound C1=CC=C2C(C(=O)OCC[N+](C)(C(C)C)C(C)C)C3=CC=CC=C3OC2=C1 VVWYOYDLCMFIEM-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 239000009223 Psyllium Substances 0.000 description 1
- 229930189077 Rifamycin Natural products 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 102100026186 Transient receptor potential cation channel subfamily A member 1 Human genes 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 235000016520 artichoke thistle Nutrition 0.000 description 1
- 235000013793 astaxanthin Nutrition 0.000 description 1
- 239000001168 astaxanthin Substances 0.000 description 1
- MQZIGYBFDRPAKN-ZWAPEEGVSA-N astaxanthin Chemical compound C([C@H](O)C(=O)C=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)C(=O)[C@@H](O)CC1(C)C MQZIGYBFDRPAKN-ZWAPEEGVSA-N 0.000 description 1
- 229940022405 astaxanthin Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- YSXKPIUOCJLQIE-UHFFFAOYSA-N biperiden Chemical compound C1C(C=C2)CC2C1C(C=1C=CC=CC=1)(O)CCN1CCCCC1 YSXKPIUOCJLQIE-UHFFFAOYSA-N 0.000 description 1
- 229960003003 biperiden Drugs 0.000 description 1
- 208000024330 bloating Diseases 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229920006037 cross link polymer Polymers 0.000 description 1
- 239000004148 curcumin Substances 0.000 description 1
- 235000012754 curcumin Nutrition 0.000 description 1
- 229940109262 curcumin Drugs 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 239000002781 deodorant agent Substances 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 210000004921 distal colon Anatomy 0.000 description 1
- 238000009506 drug dissolution testing Methods 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 235000014134 echinacea Nutrition 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001125 extrusion Methods 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 235000004611 garlic Nutrition 0.000 description 1
- 230000030136 gastric emptying Effects 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000009569 green tea Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- CSSYQJWUGATIHM-IKGCZBKSSA-N l-phenylalanyl-l-lysyl-l-cysteinyl-l-arginyl-l-arginyl-l-tryptophyl-l-glutaminyl-l-tryptophyl-l-arginyl-l-methionyl-l-lysyl-l-lysyl-l-leucylglycyl-l-alanyl-l-prolyl-l-seryl-l-isoleucyl-l-threonyl-l-cysteinyl-l-valyl-l-arginyl-l-arginyl-l-alanyl-l-phenylal Chemical compound C([C@H](N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CC=CC=C1 CSSYQJWUGATIHM-IKGCZBKSSA-N 0.000 description 1
- 229940078795 lactoferrin Drugs 0.000 description 1
- 235000021242 lactoferrin Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000002429 large intestine Anatomy 0.000 description 1
- KXGCNMMJRFDFNR-WDRJZQOASA-N linaclotide Chemical compound C([C@H](NC(=O)[C@@H]1CSSC[C@H]2C(=O)N[C@H]3CSSC[C@H](N)C(=O)N[C@H](C(N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N2)=O)CSSC[C@H](NC(=O)[C@H](C)NC(=O)[C@@H]2CCCN2C(=O)[C@H](CC(N)=O)NC3=O)C(=O)N[C@H](C(NCC(=O)N1)=O)[C@H](O)C)C(O)=O)C1=CC=C(O)C=C1 KXGCNMMJRFDFNR-WDRJZQOASA-N 0.000 description 1
- 229960000812 linaclotide Drugs 0.000 description 1
- 108010024409 linaclotide Proteins 0.000 description 1
- 235000019136 lipoic acid Nutrition 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- GVALZJMUIHGIMD-UHFFFAOYSA-H magnesium phosphate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O GVALZJMUIHGIMD-UHFFFAOYSA-H 0.000 description 1
- 239000004137 magnesium phosphate Substances 0.000 description 1
- 229910000157 magnesium phosphate Inorganic materials 0.000 description 1
- 229960002261 magnesium phosphate Drugs 0.000 description 1
- 235000010994 magnesium phosphates Nutrition 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- GLVAUDGFNGKCSF-UHFFFAOYSA-N mercaptopurine Chemical compound S=C1NC=NC2=C1NC=N2 GLVAUDGFNGKCSF-UHFFFAOYSA-N 0.000 description 1
- 229960001428 mercaptopurine Drugs 0.000 description 1
- KBOPZPXVLCULAV-UHFFFAOYSA-N mesalamine Chemical compound NC1=CC=C(O)C(C(O)=O)=C1 KBOPZPXVLCULAV-UHFFFAOYSA-N 0.000 description 1
- 229960004963 mesalazine Drugs 0.000 description 1
- 125000005395 methacrylic acid group Chemical group 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- VWZPIJGXYWHBOW-UHFFFAOYSA-N otilonium bromide Chemical compound [Br-].CCCCCCCCOC1=CC=CC=C1C(=O)NC1=CC=C(C(=O)OCC[N+](C)(CC)CC)C=C1 VWZPIJGXYWHBOW-UHFFFAOYSA-N 0.000 description 1
- 229960000426 otilonium bromide Drugs 0.000 description 1
- 235000020737 peppermint extract Nutrition 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 229940059101 polycarbophil calcium Drugs 0.000 description 1
- 230000000529 probiotic effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 229960000697 propantheline Drugs 0.000 description 1
- 229940070687 psyllium Drugs 0.000 description 1
- 230000002040 relaxant effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 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
- 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 description 1
- 229960003040 rifaximin Drugs 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000009498 subcoating Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002522 swelling effect Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229960002663 thioctic acid Drugs 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 229960005345 trimebutine Drugs 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/282—Organic compounds, e.g. fats
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
- A61K9/2846—Poly(meth)acrylates
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/288—Compounds of unknown constitution, e.g. material from plants or animals
-
- 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
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Botany (AREA)
- Zoology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
公开了结肠特异性延迟释放药物组合物，包含：a)基质，其中分散了粒度分布为100nm至1200μm的微粉化薄荷醇；b)基质a)的具有滞后时间的胃抵抗性或抗酸性pH独立的包衣。
Description
本发明涉及装载到具有胃抵抗型包衣的整体式系统中的含有掺入在羟丙基甲基纤维素亲水基质中的薄荷醇的释放改变的组合物。
本发明的组合物调节薄荷醇的活性，减少其施用频率和调控其在胃肠道的特定位置的释放。
本发明的组合物可用于治疗炎性、免疫性和/或全身性来源的肠病症，特别是治疗肠易激惹综合征。
现有技术
近年来，欧薄荷在治疗肠易激惹综合征(IBS)的症状、特别是胃肠道痛性痉挛、气胀和腹痛中的应用已经通过大量研究得以验证和证实。欧薄荷油对消化道平滑肌的解痉作用是熟知的。所述作用已经在体外和体内被不同地证实，尤其是对结肠平滑肌纤维。主要负责欧薄荷油的作用的成分是薄荷醇，其呈现出可归于以下活性机制的显著解痉作用：
-抑制在收缩机制中牵涉的、存在于平滑肌细胞上的Ca2+通道；
-结肠性激活TRPM8(瞬时受体电位通道)受体，该受体引起对结肠肌的长效放松作用(已知为清凉受体)；
-抑制TRPA1受体，该受体引起结肠近端和远端收缩。
鉴于这些性质，一个特别期望的目标是薄荷醇的具有适宜滞后时间直至到达小肠的远端部分、从远端回肠开始的结肠特异性释放，由此确保了产品在整个结肠道中缓慢、逐渐和恒定的释放。
以胃抵抗性包衣为特征的薄荷精油制剂是已知的和在市场上已经是可获得的。但是，已知制剂的释放性质是不满意的，因为它没有保证在整个结肠道中均匀释放。
US 2012/207842公开了具有胃抵抗性包衣的多颗粒延迟释放系统(2小时，pH1.2)，其在中性pH快速释放(2小时内最多超过80％薄荷醇)。核不呈现出释放改变的系统，而是立即释放或适度释放控制(45分钟至2小时)。所述文献要求在核和底包衣中使用羟丙基甲基纤维素，但目的不是控制释放，而是作为粘合剂以获得颗粒和在薄膜包衣中作为包衣剂。
WO 01/76392公开了含有大蒜作为活性成分以及肠溶包衣的组合物。该活性成分在小肠中立即释放。该组合物可以含有欧薄荷提取物(不是纯薄荷醇)作为除臭剂。薄荷油存在于外层肠溶薄膜衣中，因此未进行任何在肠环境中的释放控制，因此提取物在肠环境中被立即释放。因此，该文献没有公开薄荷醇的结肠特异性延迟释放制剂，也没有公开其中薄荷醇分散于亲水基质中的制剂。
CN 102008547公开了用丙烯酸树脂包衣的含有圆叶薄荷(Mentharotundifoliae)油(其具有非显著的薄荷醇含量)的胶囊。因此，其不仅没有涉及结晶薄荷醇，而且该文献中所述的制剂不具有活性成分在结肠中延迟释放的任何作用，仅仅是胃抵抗性的。
发明描述
现在已经发现，采用包含如下的整体式药物组合物可以获得最适宜的薄荷醇结肠特异性缓慢释放：
a)含有羟丙基甲基纤维素的核，其中分散了研磨、共研磨或微粉化形式的薄荷醇，粒度为100nm至1200μm；
b)核a)的胃抵抗型包衣。
以具有整体式基质的核为特征的本发明的制剂能够调控、控制和减缓活性成分在8-24小时内的释放。核的胃抵抗型包衣在pH<1.2-5.5的条件下阻止了体外释放达至少2小时。
胃抵抗型包衣通常由纤维素衍生物、邻苯二甲酸纤维素、琥珀酸酯、甲基丙烯酸或聚甲基丙烯酸聚合物、虫胶或海藻酸组成，优选由虫胶和羟丙基甲基纤维素、或乙基纤维素连同海藻酸、或聚甲基丙烯酸(pH-依赖性)、或简单的乙基纤维素和/或羟丙基甲基纤维素(pH-独立/滞后时间)组成。虫胶和羟丙基甲基纤维素的混合物是特别优选的。
基质核包涂了足以保证其在从核释放活性成分之前在胃液和肠液中保持完整达至少2-4小时(滞后时间)的量的聚合物/树脂。为了减少胃排空时间差异的影响，制剂可以在基质核(pH-独立)外和在纤维素膜包衣(pH-独立)外包括另外的胃抵抗型包衣(pH-依赖性)以进一步延迟生物流体与释放改变的核之间的接触(延时释放)。
在这种方式中，该系统阻止了胃-空肠通过时间期间的早期释放，获得了一直到24小时的缓慢释放以确保药物在大肠的上升束、横向束和下行束的均匀分布。
因此，本发明的组合物与通常的延迟释放形式(胃抵抗型和/或具有滞后时间)是不同的，后者可以到达回肠的远端部分和/或结肠的开始部分，但是然后快速释放活性组分而没有在结肠道中均匀分布。
基质核使用具有不同流变学特征(粘度/膨胀性质)的羟丙基甲基纤维素允许以逐渐的程序方式调控释放达8-24小时。根据本发明可以使用的羟丙基甲基纤维素具有3-200,000mPs、优选30-150,000、更优选50-100,000的表观粘度，所述表观粘度于20℃在2％水性溶液中测定。可以使用单一类型的羟丙基甲基纤维素或者至少两种类型的具有不同粘度的羟丙基甲基纤维素的混合物。羟丙基甲基纤维素在市场上可以从Dow Chemical以商标Methocel获得，或者从Ashland以商标Benecel获得。羟丙基甲基纤维素的优选实例有具有与市售产品Methocel K100lv、K15M、K4M和K100M相同的特征的那些。特别优选使用具有与Methocel K100lv相似的78至117mPas的粘度的羟丙基甲基纤维素。
本发明的组合物通常将含有10-1200mg薄荷醇、优选50-200mg薄荷醇的单位剂量。
薄荷醇和亲水基质的重量比为1:5至4:1(优选1:3)。
本发明的组合物还可以含有其它赋形剂，例如湿润剂、离子或非离子型表面活性剂、崩解剂、超崩解剂、交联聚合物、络合剂和润滑剂。
所述赋形剂的实例包括磷脂、卵磷脂、月桂硫酸钠、山梨坦酯、蔗糖棕榈酸酯、月桂肌氨酸钠、胆酸、泊洛沙姆、环糊精、淀粉、淀粉羟乙酸钠、交联羧甲基纤维素和交联聚乙烯吡咯烷酮。
羟丙基甲基纤维素的亲水基质可以任选地通过添加亲脂性成分(脂肪酸、脂肪醇、甘油三酯)、水溶性成分(多元醇、甘露醇、乳糖、海藻糖)、水可分散性成分(微晶纤维素)或水不溶性成分(磷酸氢钙、钙和镁盐)进行修饰以调控释放动力学。
本发明的组合物使得薄荷醇在治疗肠易激惹综合征中的药理学作用最大化，这是因为它们能够将活性成分运送到结肠中和特别是在结肠中释放活性成分。胃抵抗性包衣必须保证结构在pH1.2保持约1-2小时，并且在随后8-2小时在pH7.2保证控释性质，由此确保从结肠的上行束至横向和下行束的药理学覆盖区。
对于预期应用，重要的是保证从回肠末端通道开始并在整个结肠道继续的控制释放。还有必要保证随时间推移释放的量的一定均匀性，同时当已经释放一定比例的活性成分时允许其在局部和全身水平的活性。因此，本发明的组合物可特别用于治疗急性和慢性胃肠病症如肠易激惹综合征(IBS)、腹泻、便秘、节段性回肠炎、溃疡性结肠炎和一般性的炎性肠病(IBD)。
常规技术如直接压片、湿法制粒、干法压片/制粒和熔融制粒可用于制备本发明的组合物。
由于薄荷醇作为大结晶存在，所以它不能原样用于制备和生产不同的药物形式，因此必须通过研磨和/或微粉化和/或共研磨单独或装载在一些惰性稀释赋形剂中的产品而进行活化步骤。
将产品(最初以数厘米尺寸的半透明晶体的形式存在)适宜地研磨、微粉化和/或与其它功能性赋形剂如纤维素、淀粉、糊精、磷酸钙、多元醇、胶体二氧化硅和其它稀释剂共研磨，以获得具有100nm至1200μm、优选50至700μm尺寸的产品。
因此，采用适宜的湿法或干法制粒技术、直接分配、直接压片、共研磨、熔融制粒或挤出制粒在加入赋形剂如湿润剂、表面活性剂、崩解剂、超崩解剂、助流剂、无粘性物质或润滑剂的情况下将产品掺入亲水基质中。
然后将由具有胃抵抗性和/或在不同肠pH的释放性质(pH-依赖性)和/或pH-独立的滞后时间性质(延迟释放)的材料组成的外包衣应用于如此获得的核。根据本发明的一般实施方案，首先制备了含有一种或多种类型的羟丙基甲基纤维素的亲水基质，其中分散了微粉化、研磨或共研磨的薄荷醇。然后通过不同药物方法加入稀释产品和使其可操作所需的任意功能性赋形剂。活性成分:基质的比例可以为1:1至1:9，活性成分:赋形剂的比例应当通常不超过1:4；最佳量为0.1％至50％。
可以向该混合物中加入可变量的至多50％的稀释剂、润滑剂(0.5-3％)、助流剂(0.5-3％)、崩解剂和超崩解剂(0.1-40％)和络合剂(0.1-40％)。
本发明的组合物还可以含有其它具有协同、补充或在其它方面有用的活性的活性成分。所述活性成分的实例包括益生菌(乳杆菌属(lactobacilli),双歧杆菌属(bifidobacteria))、消化酶(肠液)、益生元(丁酸盐、丙酸盐、中长链脂肪酸、ω-3脂肪酸或酯)、纤维(欧车前、瓜尔胶、阿拉伯纤维、聚卡波非钙)、解痉药(曲美布汀及其盐、奥替溴铵及其它盐、双环胺及其盐、替罗拉胺、丙胺太林及其盐、比哌立登及其盐、辛托品及其盐、美金刚和尿多灵(ditropan))、在IBS和IBD中具有活性的药物如抗炎剂(美沙拉嗪、皮质类固醇、硫唑嘌呤、巯嘌呤、α-硫辛酸)、在IBS中具有活性的药物(卢比前列通、利那洛肽(linaclotide))、植物来源的提取物或活性成分(洋蓟、虾青素、洋甘菊、姜黄素、乳香属、绿茶、紫锥花属)、乳铁蛋白和具有局部作用的抗生素如利福昔明和利福霉素。
就溶出性质而言，上述组合物与水或肠生物流体之间的接触产生了活性成分的延迟、位置特异性的释放。结构中存在的赋形剂和聚合物调节了系统的可润湿性和薄荷醇在有限释放范围内的均匀溶出，由此促进了其在胃肠道中的局限性活性和连续逐渐的吸收。
以下实施例更详细地解释了本发明。
实施例1
将50g活化的薄荷醇与200g磷酸氢钙、200mg微晶纤维素和150g甘露醇一起加入混合器/造粒机中。
向相同体系中依次加入2g交聚维酮、8g卵磷脂和150g羟丙基甲基纤维素(HPMCK100lv)。
将各成分混合直至基质均匀分散，然后依次加入5g硬脂酸镁和5g胶体二氧化硅。
将最终混合物压制成770mg/片的单位重，以施用50mg活性成分/片。
然后将所得片剂用基于30g虫胶(25％)、12g羟丙基甲基纤维素和6g甘油的胃抵抗性溶液/混悬液进行薄膜包衣，获得平均重为818mg的片剂。
当于pH 1.2进行崩解实验时，片剂保持完整达至少2小时。当于pH 7.2进行溶出试验时，它们呈现出以下释放性质：在60分钟后不超过20％，在240分钟后不超过60％，在480分钟后不超过80％；在任何事件中，该值在24小时后必须>70％。
实施例2
将50g活化的薄荷醇装入造粒机/匀化器中，加入55g甘露醇。
将100g羟丙基甲基纤维素(HPMC K 100lv)、55g羟丙基甲基纤维素(K4M)和50mg微晶纤维素加入相同造粒机中。
将各成分混合直至基质均匀分散，然后依次加入210g磷酸钙、3g硬脂酸镁和5g胶体二氧化硅。
将最终混合物压制成530mg/片的单位重，以施用50mg活性成分/片。
然后将所得片剂用基于20g虫胶(25％)20、8g羟丙基甲基纤维素和2g甘油的胃抵抗性溶液/混悬液进行薄膜包衣，获得平均重为560mg的片剂。
当于pH 1.2进行崩解实验时，片剂保持完整达至少2小时。当于pH 7.2进行溶出试验时，它们呈现出以下释放性质：在60分钟后不超过10％，在240分钟后不超过40％，在480分钟不超过70％；在任何事件中，该值在24小时后必须>70％。
实施例3
将800g薄荷醇装入造粒机/匀化器中，加入200g羟丙基甲基纤维素(K100lv)、200g羟丙基甲基纤维素(K15M)、480g甘露醇和252g微晶纤维素。
将各成分混合至少15分钟以获得均匀混合物。
然后依次加入8g交联羧甲基纤维素、40g卵磷脂、40g胶体二氧化硅和20g硬脂酸镁。
将最终混合物压制成510mg/片的单位重，以施用200mg活性成分/片。
然后将所得核用500g虫胶(aquagold 25％)、50g羟丙基甲基纤维素和25g甘油进行包衣。获得具有约50mg包衣/片的胃抵抗性薄膜包衣。
当于pH1.2、然后于pH 7.2进行溶出试验时，该片剂呈现出以下释放性质：pH 1.2:在120分钟后0％；pH 7.2：在60分钟后不超过25％、在180分钟后不超过50％和在8小时后不超过80％；在12小时后>80％。实施例4
将800g薄荷醇装入造粒机/匀化器中，加入200g羟丙基甲基纤维素、200g聚氧乙烯氧化物(PEO-20NF)、480g甘露醇和252g微晶纤维素。
将各成分混合至少15分钟以获得均匀基质。
然后依次加入8g交联羧甲基纤维素、40g卵磷脂、40g胶体二氧化硅和20g硬脂酸镁。
将最终混合物压制成510mg/片的单位重，以施用200mg活性成分/片。
然后将所得核用含有80g乙基纤维素、16g海藻酸钠、2g二氧化钛和2g硬脂酸的水性分散液进行包衣。获得具有约25mg包衣/片的薄膜包衣。
当进行溶出实验时，片剂呈现出以下释放性质：pH 1.2：在120分钟后<10％；pH7.2：在60分钟后不超过25％、在180分钟后不超过60％和在8小时后不超过80％；在24小时后>80％。
实施例5
将500g活化的薄荷醇与350g磷酸氢钙一起装入混合器/造粒机中。
向相同系统中依次加入2g交聚维酮和150g亲水基质羟丙基甲基纤维素(HPMCK15M)。
将各成分混合直至基质均匀分散，然后依次加入5g硬脂酸镁、5g胶体二氧化硅和8g山嵛酸甘油酯。
将最终混合物压制成1020mg/片的单位重，以施用500mg活性成分/片。
然后将所得片剂用基于160g虫胶(25％)、20g羟丙基甲基纤维素和8g甘油的胃抵抗性溶液/混悬液进行薄膜包衣。
当于pH 1.2进行崩解实验时，片剂保持完整达至少2小时。当于pH 7.2进行溶出试验时，它们呈现出以下释放性质：在60分钟后不超过35％，在240分钟后不超过65％，在480分钟后不超过80％；在任何事件中，该值在24小时后必须>80％。
Claims (13)
1.整体式结肠特异性延迟释放药物组合物，包含：
a)含有亲水基质羟丙基甲基纤维素的核，其中分散了研磨、共研磨或微粉化形式的薄荷醇，粒度为100nm至1200μm，其中薄荷醇:羟丙基甲基纤维素的重量比为1:5-4:1，和其中核中的羟丙基甲基纤维素具有50-100,000mPas的表观粘度，所述表观粘度于20℃在2％水溶液中测定；
b)核a)的胃抵抗性包衣。
2.根据权利要求1的组合物，其中所述核包含至少两种具有不同表观粘度值的羟丙基甲基纤维素的混合物。
3.根据权利要求1的组合物，包含仅一种具有80至120mPas的表观粘度的羟丙基甲基纤维素，所述表观粘度于20℃在2％水溶液中测定。
4.根据权利要求1-3任一项的组合物，其中胃抵抗性包衣包含羟丙基甲基纤维素、乙基纤维素、乙酸邻苯二甲酸纤维素、甲基丙烯酸聚合物、虫胶、海藻酸或其混合物。
5.根据权利要求1-3任一项的组合物，其中胃抵抗性包衣由虫胶和羟丙基甲基纤维素、或乙基纤维素和海藻酸、或聚甲基丙烯酸酯或乙酸邻苯二甲酸纤维素组成。
6.根据权利要求1-3任一项的组合物，包含50-1200mg薄荷醇。
7.根据权利要求1-3任一项的组合物，其中薄荷醇:羟丙基甲基纤维素的重量比为1:3。
8.根据权利要求1-3任一项的组合物，还包含选自湿润剂、离子或非离子型表面活性剂、水溶性稀释剂、水可分散性稀释剂、水不溶性稀释剂、崩解剂、润滑剂、助流剂和着色剂的赋形剂。
9.根据权利要求8的组合物，其中所述赋形剂选自磷脂、月桂硫酸钠、山梨坦酯、蔗糖棕榈酸酯、月桂肌氨酸钠、胆酸、泊洛沙姆、淀粉、淀粉羟乙酸钠、交联羧甲基纤维素、交联聚乙烯吡咯烷酮、多元醇、微晶纤维素、钙盐和镁盐。
10.根据权利要求9的组合物，其中所述的钙盐是磷酸氢钙。
11.根据权利要求8的组合物，其中所述赋形剂选自卵磷脂。
12.根据权利要求1-3任一项的组合物，还包含选自如下的一种或多种成分：益生菌、消化酶、益生元、纤维、解痉药、抗炎剂、IBS-和IBD-活性药物、植物来源的提取物或活性成分、局部抗生素。
13.权利要求1-12任一项的组合物在制备用于治疗肠易激惹综合征和炎性肠病的产品中的用途。
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT002066A ITMI20132066A1 (it) | 2013-12-11 | 2013-12-11 | Sistemi terapeutici a rilascio modificato per la somministrazione orale di mentolo nel trattamento delle malattie intestinali |
| ITMI2013A002066 | 2013-12-11 | ||
| PCT/IB2014/066763 WO2015087258A1 (en) | 2013-12-11 | 2014-12-10 | Modified-release therapeutic systems for oral administration of menthol in the treatment of intestinal disorders |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105828807A CN105828807A (zh) | 2016-08-03 |
| CN105828807B true CN105828807B (zh) | 2021-02-02 |
Family
ID=50001133
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201480067078.3A Expired - Fee Related CN105828807B (zh) | 2013-12-11 | 2014-12-10 | 用于在治疗肠病症中口服施用薄荷醇的释放改变的治疗系统 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US10328035B2 (zh) |
| EP (1) | EP3079673B1 (zh) |
| JP (1) | JP6471165B2 (zh) |
| KR (1) | KR102296850B1 (zh) |
| CN (1) | CN105828807B (zh) |
| CA (1) | CA2933309A1 (zh) |
| ES (1) | ES2698132T3 (zh) |
| IT (1) | ITMI20132066A1 (zh) |
| RU (1) | RU2683645C1 (zh) |
| WO (1) | WO2015087258A1 (zh) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2020004107A (es) | 2017-10-25 | 2020-07-24 | Chiesi Farm Spa | Tabletas de deferiprona de liberacion retrasada y metodos de uso de las mismas. |
| KR102070970B1 (ko) | 2018-05-18 | 2020-01-29 | 한국한의학연구원 | 단풍나무 추출물을 포함하는 장 질환의 예방 또는 치료용 조성물 |
| CN110772502B (zh) * | 2019-12-06 | 2023-03-28 | 上海市肺科医院 | 一种用于治疗过敏性鼻炎的组合物及制备方法和应用 |
| CN111297889A (zh) * | 2020-02-28 | 2020-06-19 | 奥纳斯(北京)医药科技有限公司 | 一种对胃肠道痉挛和胆道系统痉挛均具有抑制作用的组合物、其水溶液及其制法 |
| IT202000005782A1 (it) * | 2020-03-18 | 2021-09-18 | Dpl Pharma S P A | Formulazioni farmaceutiche a rilascio controllato per il trattamento di infezioni intestinali |
| US12016851B2 (en) | 2022-04-11 | 2024-06-25 | Chiesi Farmaceutici S.P.A. | Modified release pharmaceutical formulations comprising deferiprone |
| US12016850B2 (en) | 2022-04-11 | 2024-06-25 | Chiesi Farmaceutici S.P.A. | Modified release pharmaceutical formulations comprising deferiprone |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101590020A (zh) * | 2008-05-30 | 2009-12-02 | 上海新菲尔生物制药工程技术有限公司 | 一种对氨基水杨酸钠结肠定位给药系统 |
| CN101721385A (zh) * | 2008-10-13 | 2010-06-09 | 重庆医药工业研究院有限责任公司 | 一种美沙拉嗪口服控释药物组合物 |
| US20120207842A1 (en) * | 2011-02-11 | 2012-08-16 | Shah Syed M | Multiparticulate l-menthol formulations and related methods |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5397573A (en) * | 1993-06-04 | 1995-03-14 | The Procter & Gamble Company | Laxative compositions |
| AUPQ672800A0 (en) * | 2000-04-06 | 2000-05-04 | Natraherbal Pty Ltd | Garlic supplement for deodoriser |
| US6919348B2 (en) * | 2002-05-02 | 2005-07-19 | Edward T. Wei | Therapeutic 1,2,3,6-tetrahydropyrimidine-2-one compositions and methods therewith |
| CA2498931A1 (en) * | 2002-09-16 | 2004-03-25 | Wyeth | Delayed release formulations for oral administration of a polypeptide therapeutic agent and methods of using same |
| FR2845289B1 (fr) * | 2002-10-04 | 2004-12-03 | Ethypharm Sa | Spheroides, procede de preparation et compositions pharmaceutiques. |
| CA2576386A1 (en) * | 2004-08-13 | 2006-02-16 | Boehringer Ingelheim International Gmbh | Extended release pellet formulation containing pramipexole or a pharmaceutically acceptable salt thereof, method for manufacturing the same and use thereof |
| WO2007143158A2 (en) * | 2006-06-01 | 2007-12-13 | Schering-Plough Healthcare Products, Inc. | Sustained release pharmaceutical formulation comprising phenylephrine |
| JP5395052B2 (ja) * | 2007-03-23 | 2014-01-22 | モレキュラー リサーチ センター インコーポレイテッド | 炎症を処置するための組成物および方法 |
| US20110002986A1 (en) * | 2009-07-02 | 2011-01-06 | Hercules Incorporated | Stable Shellac Enteric Coating Formulation for Nutraceutical and Pharmaceutical Dosage Forms |
| CN102008547B (zh) * | 2010-12-07 | 2012-10-17 | 单承仪 | 一种应用植物留兰香提取物治疗习惯性便秘的药物及制备方法 |
-
2013
- 2013-12-11 IT IT002066A patent/ITMI20132066A1/it unknown
-
2014
- 2014-12-10 CN CN201480067078.3A patent/CN105828807B/zh not_active Expired - Fee Related
- 2014-12-10 CA CA2933309A patent/CA2933309A1/en not_active Abandoned
- 2014-12-10 WO PCT/IB2014/066763 patent/WO2015087258A1/en active Application Filing
- 2014-12-10 ES ES14830618T patent/ES2698132T3/es active Active
- 2014-12-10 RU RU2016122897A patent/RU2683645C1/ru active
- 2014-12-10 EP EP14830618.6A patent/EP3079673B1/en active Active
- 2014-12-10 KR KR1020167015412A patent/KR102296850B1/ko active IP Right Grant
- 2014-12-10 JP JP2016539146A patent/JP6471165B2/ja not_active Expired - Fee Related
- 2014-12-10 US US15/103,192 patent/US10328035B2/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101590020A (zh) * | 2008-05-30 | 2009-12-02 | 上海新菲尔生物制药工程技术有限公司 | 一种对氨基水杨酸钠结肠定位给药系统 |
| CN101721385A (zh) * | 2008-10-13 | 2010-06-09 | 重庆医药工业研究院有限责任公司 | 一种美沙拉嗪口服控释药物组合物 |
| US20120207842A1 (en) * | 2011-02-11 | 2012-08-16 | Shah Syed M | Multiparticulate l-menthol formulations and related methods |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20160094977A (ko) | 2016-08-10 |
| US20180133166A1 (en) | 2018-05-17 |
| RU2683645C1 (ru) | 2019-04-01 |
| KR102296850B1 (ko) | 2021-09-01 |
| US10328035B2 (en) | 2019-06-25 |
| CN105828807A (zh) | 2016-08-03 |
| ES2698132T3 (es) | 2019-01-31 |
| EP3079673B1 (en) | 2018-09-19 |
| WO2015087258A8 (en) | 2015-10-29 |
| WO2015087258A1 (en) | 2015-06-18 |
| EP3079673A1 (en) | 2016-10-19 |
| JP6471165B2 (ja) | 2019-02-13 |
| ITMI20132066A1 (it) | 2015-06-12 |
| CA2933309A1 (en) | 2015-06-18 |
| JP2016540019A (ja) | 2016-12-22 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105828807B (zh) | 用于在治疗肠病症中口服施用薄荷醇的释放改变的治疗系统 | |
| US10828268B2 (en) | Modified-release therapeutic systems for oral administration of curcumin in the treatment of intestinal disorders | |
| US11090279B2 (en) | Delayed release cysteamine bead formulation, and methods of making and using same | |
| JP2016531912A (ja) | 低１日用量で投与するためのフマル酸ジメチルを含む医薬組成物 | |
| AU2019329905B2 (en) | Vitamin D pediatric dosage forms, methods of making and using | |
| CN113382720B (zh) | 用于美沙拉嗪或其衍生物施用的固体口服药物组合物 | |
| RU2738114C2 (ru) | Пероральные фармацевтические композиции никотинамида | |
| CN114845705A (zh) | 用于治疗胃肠疾病的口服固体大麻素油组合物 | |
| US20230181545A1 (en) | Controlled-release pharmaceutical formulations for treatment of intestinal infections | |
| US20230330076A1 (en) | Controlled release formulations of flavoxate and process for preparation thereof | |
| WO2021229420A1 (en) | Solid oral compositions comprising composite monolithic matrices for chronotropic administration in the gastrointestinal tract of foods, diet supplements, nutraceuticals and medical devices | |
| Sanghi et al. | FORMULATION AND EVALUTATION OF DUAL RELEASE MULTIPLE UNIT TABLET FORMULATION | |
| JP2012107058A (ja) | 複数のコーティングを有する医薬剤形 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20210202 Termination date: 20211210 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |