CA2538099A1 - Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin - Google Patents
Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin Download PDFInfo
- Publication number
- CA2538099A1 CA2538099A1 CA002538099A CA2538099A CA2538099A1 CA 2538099 A1 CA2538099 A1 CA 2538099A1 CA 002538099 A CA002538099 A CA 002538099A CA 2538099 A CA2538099 A CA 2538099A CA 2538099 A1 CA2538099 A1 CA 2538099A1
- Authority
- CA
- Canada
- Prior art keywords
- minitablets
- rapamycin
- salt
- coating
- composition
- 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.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 111
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 title claims abstract description 106
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 title claims abstract description 99
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 title claims abstract description 84
- 229960000951 mycophenolic acid Drugs 0.000 title claims abstract description 77
- 229960002930 sirolimus Drugs 0.000 title claims abstract description 67
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 title claims abstract description 65
- 239000000651 prodrug Substances 0.000 claims abstract description 47
- 229940002612 prodrug Drugs 0.000 claims abstract description 47
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 239000008185 minitablet Substances 0.000 claims description 114
- 239000008187 granular material Substances 0.000 claims description 57
- 239000008188 pellet Substances 0.000 claims description 53
- 239000011324 bead Substances 0.000 claims description 50
- 229960004866 mycophenolate mofetil Drugs 0.000 claims description 49
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims description 47
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 42
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 42
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 42
- 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 41
- 239000003826 tablet Substances 0.000 claims description 39
- 239000002702 enteric coating Substances 0.000 claims description 36
- 238000009505 enteric coating Methods 0.000 claims description 36
- 239000013543 active substance Substances 0.000 claims description 17
- 239000011859 microparticle Substances 0.000 claims description 17
- 239000007884 disintegrant Substances 0.000 claims description 16
- 238000009498 subcoating Methods 0.000 claims description 16
- 239000011230 binding agent Substances 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 239000000314 lubricant Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 239000000945 filler Substances 0.000 claims description 9
- 210000002784 stomach Anatomy 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 8
- 239000004480 active ingredient Substances 0.000 claims description 7
- 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
- 206010052779 Transplant rejections Diseases 0.000 claims description 5
- 239000001856 Ethyl cellulose Substances 0.000 claims description 4
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 4
- 229920001249 ethyl cellulose Polymers 0.000 claims description 4
- 210000000214 mouth Anatomy 0.000 claims description 4
- 210000000813 small intestine Anatomy 0.000 claims description 4
- 210000000056 organ Anatomy 0.000 claims description 3
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- 230000001413 cellular effect Effects 0.000 claims description 2
- 230000009261 transgenic effect Effects 0.000 claims description 2
- 238000000576 coating method Methods 0.000 description 104
- 239000011248 coating agent Substances 0.000 description 92
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- 229940126062 Compound A Drugs 0.000 description 46
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 46
- 239000003814 drug Substances 0.000 description 40
- 229940079593 drug Drugs 0.000 description 39
- 239000002775 capsule Substances 0.000 description 37
- 239000004615 ingredient Substances 0.000 description 32
- 239000007962 solid dispersion Substances 0.000 description 28
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- -1 alkali metal salts Chemical class 0.000 description 19
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 17
- 239000003795 chemical substances by application Substances 0.000 description 14
- 239000006185 dispersion Substances 0.000 description 13
- 238000009472 formulation Methods 0.000 description 13
- 239000000454 talc Substances 0.000 description 13
- 229910052623 talc Inorganic materials 0.000 description 13
- 239000001069 triethyl citrate Substances 0.000 description 12
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 12
- 235000013769 triethyl citrate Nutrition 0.000 description 12
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 11
- 229920003081 Povidone K 30 Polymers 0.000 description 11
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 11
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 description 11
- 238000005469 granulation Methods 0.000 description 10
- 230000003179 granulation Effects 0.000 description 10
- 235000019359 magnesium stearate Nutrition 0.000 description 10
- 239000008108 microcrystalline cellulose Substances 0.000 description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 9
- 239000001828 Gelatine Substances 0.000 description 9
- 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 9
- 238000001035 drying Methods 0.000 description 9
- 229920000159 gelatin Polymers 0.000 description 9
- 235000019322 gelatine Nutrition 0.000 description 9
- 239000008101 lactose Substances 0.000 description 9
- 239000002609 medium Substances 0.000 description 9
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 9
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 8
- 239000002202 Polyethylene glycol Substances 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 238000002156 mixing Methods 0.000 description 8
- 229920001223 polyethylene glycol Polymers 0.000 description 8
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 229920002472 Starch Polymers 0.000 description 7
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 7
- 229960000913 crospovidone Drugs 0.000 description 7
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 7
- 235000019698 starch Nutrition 0.000 description 7
- YQEMORVAKMFKLG-UHFFFAOYSA-N 2-stearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 6
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
- 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 6
- 239000003963 antioxidant agent Substances 0.000 description 6
- 235000006708 antioxidants Nutrition 0.000 description 6
- 229960003444 immunosuppressant agent Drugs 0.000 description 6
- 239000003018 immunosuppressive agent Substances 0.000 description 6
- 229910052708 sodium Inorganic materials 0.000 description 6
- 229960002622 triacetin Drugs 0.000 description 6
- GUBGYTABKSRVRQ-DCSYEGIMSA-N Beta-Lactose Chemical compound OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-DCSYEGIMSA-N 0.000 description 5
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 5
- 229910002054 SYLOID® 244 FP SILICA Inorganic materials 0.000 description 5
- 229920002301 cellulose acetate Polymers 0.000 description 5
- 150000001875 compounds Chemical class 0.000 description 5
- 229920001577 copolymer Chemical class 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 5
- PSGAAPLEWMOORI-PEINSRQWSA-N medroxyprogesterone acetate Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](OC(C)=O)(C(C)=O)CC[C@H]21 PSGAAPLEWMOORI-PEINSRQWSA-N 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 5
- 229920000858 Cyclodextrin Polymers 0.000 description 4
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 4
- 229920003135 Eudragit® L 100-55 Polymers 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 4
- 229930006000 Sucrose Natural products 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
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000009246 food effect Effects 0.000 description 4
- 235000021471 food effect Nutrition 0.000 description 4
- 238000000227 grinding Methods 0.000 description 4
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 description 4
- 230000001506 immunosuppresive effect Effects 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 4
- 239000004014 plasticizer Substances 0.000 description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 4
- 229940069328 povidone Drugs 0.000 description 4
- 238000012545 processing Methods 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
- 238000001694 spray drying Methods 0.000 description 4
- 229960004793 sucrose Drugs 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 125000005591 trimellitate group Chemical group 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 3
- 229920002785 Croscarmellose sodium Polymers 0.000 description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 206010003246 arthritis Diseases 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 229960001681 croscarmellose sodium Drugs 0.000 description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 3
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 3
- 230000001861 immunosuppressant effect Effects 0.000 description 3
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 235000019426 modified starch Nutrition 0.000 description 3
- 229940014456 mycophenolate Drugs 0.000 description 3
- 125000001557 phthalyl group Chemical group C(=O)(O)C1=C(C(=O)*)C=CC=C1 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000001681 protective effect Effects 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 229940032147 starch Drugs 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 229920003169 water-soluble polymer Polymers 0.000 description 3
- BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 description 2
- 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 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Natural products OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
- 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 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 235000019759 Maize starch Nutrition 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 2
- 239000004698 Polyethylene Substances 0.000 description 2
- 229920002562 Polyethylene Glycol 3350 Polymers 0.000 description 2
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 2
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000001154 acute effect Effects 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229910052782 aluminium Inorganic materials 0.000 description 2
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 2
- 208000007502 anemia Diseases 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229920001400 block copolymer Polymers 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 239000007931 coated granule Substances 0.000 description 2
- 239000008199 coating composition Substances 0.000 description 2
- 239000008119 colloidal silica Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 201000001981 dermatomyositis Diseases 0.000 description 2
- 235000013681 dietary sucrose Nutrition 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 238000001125 extrusion Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009477 fluid bed granulation Methods 0.000 description 2
- 210000001035 gastrointestinal tract Anatomy 0.000 description 2
- 125000005456 glyceride group Chemical group 0.000 description 2
- 238000009478 high shear granulation Methods 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 238000009476 low shear granulation Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- CXMXRPHRNRROMY-UHFFFAOYSA-N n-Decanedioic acid Natural products OC(=O)CCCCCCCCC(O)=O CXMXRPHRNRROMY-UHFFFAOYSA-N 0.000 description 2
- KSCKTBJJRVPGKM-UHFFFAOYSA-N octan-1-olate;titanium(4+) Chemical compound [Ti+4].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-].CCCCCCCC[O-] KSCKTBJJRVPGKM-UHFFFAOYSA-N 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 229920000573 polyethylene Polymers 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- QFMKPDZCOKCBAQ-NFCVMBANSA-N sar943-nxa Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)CC1 QFMKPDZCOKCBAQ-NFCVMBANSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 235000012239 silicon dioxide Nutrition 0.000 description 2
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 2
- 229920003109 sodium starch glycolate Polymers 0.000 description 2
- 239000008109 sodium starch glycolate Substances 0.000 description 2
- 229940079832 sodium starch glycolate Drugs 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 2
- 229950009819 zotarolimus Drugs 0.000 description 2
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 description 1
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical class CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound 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 description 1
- DJENHUUHOGXXCB-UHFFFAOYSA-N 2-butyl-6-methoxyphenol Chemical compound CCCCC1=CC=CC(OC)=C1O DJENHUUHOGXXCB-UHFFFAOYSA-N 0.000 description 1
- PTBDIHRZYDMNKB-UHFFFAOYSA-M 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoate Chemical compound OCC(C)(CO)C([O-])=O PTBDIHRZYDMNKB-UHFFFAOYSA-M 0.000 description 1
- WNWVKZTYMQWFHE-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound [CH2]CN1CCOCC1 WNWVKZTYMQWFHE-UHFFFAOYSA-N 0.000 description 1
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
- 229910002012 Aerosil® Inorganic materials 0.000 description 1
- 208000032467 Aplastic anaemia Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 206010008909 Chronic Hepatitis Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 241000834287 Cookeolus japonicus Species 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 102100028675 DNA polymerase subunit gamma-2, mitochondrial Human genes 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 239000001692 EU approved anti-caking agent Substances 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 229920003136 Eudragit® L polymer Polymers 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000009329 Graft vs Host Disease Diseases 0.000 description 1
- 208000003807 Graves Disease Diseases 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 206010019755 Hepatitis chronic active Diseases 0.000 description 1
- 101000837415 Homo sapiens DNA polymerase subunit gamma-2, mitochondrial Proteins 0.000 description 1
- GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 description 1
- 206010021245 Idiopathic thrombocytopenic purpura Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 208000029523 Interstitial Lung disease Diseases 0.000 description 1
- 208000012528 Juvenile dermatomyositis Diseases 0.000 description 1
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 1
- 208000004883 Lipoid Nephrosis Diseases 0.000 description 1
- 239000004368 Modified starch Substances 0.000 description 1
- 239000008118 PEG 6000 Substances 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 102100027913 Peptidyl-prolyl cis-trans isomerase FKBP1A Human genes 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 206010065159 Polychondritis Diseases 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 229920002584 Polyethylene Glycol 6000 Polymers 0.000 description 1
- 229920003110 Primojel Polymers 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
- 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 241000187747 Streptomyces Species 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 230000006052 T cell proliferation Effects 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 208000016807 X-linked intellectual disability-macrocephaly-macroorchidism syndrome Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-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)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 HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000002280 amphoteric surfactant Substances 0.000 description 1
- 229910052925 anhydrite Inorganic materials 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000003945 anionic surfactant Substances 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002682 anti-psoriatic effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 239000003911 antiadherent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003289 ascorbyl group Chemical group [H]O[C@@]([H])(C([H])([H])O*)[C@@]1([H])OC(=O)C(O*)=C1O* 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 201000003710 autoimmune thrombocytopenic purpura Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000003613 bile acid Substances 0.000 description 1
- 239000003833 bile salt Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010322 bone marrow transplantation Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000004067 bulking agent Substances 0.000 description 1
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 201000010415 childhood type dermatomyositis Diseases 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000005354 coacervation Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000007771 core particle Substances 0.000 description 1
- 230000001085 cytostatic effect Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940031954 dibutyl sebacate Drugs 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- SUPCQIBBMFXVTL-UHFFFAOYSA-N ethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)C(C)=C SUPCQIBBMFXVTL-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 208000024908 graft versus host disease Diseases 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 230000002949 hemolytic effect Effects 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 235000013902 inosinic acid Nutrition 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000002563 ionic surfactant Substances 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 description 1
- 229950007856 mofetil Drugs 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 229920000191 poly(N-vinyl pyrrolidone) Polymers 0.000 description 1
- 229940113125 polyethylene glycol 3000 Drugs 0.000 description 1
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 1
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229920003133 pregelled starch Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 229910052705 radium Inorganic materials 0.000 description 1
- HCWPIIXVSYCSAN-UHFFFAOYSA-N radium atom Chemical compound [Ra] HCWPIIXVSYCSAN-UHFFFAOYSA-N 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000661 sodium alginate Chemical class 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical compound [Na+].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 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 229940083575 sodium dodecyl sulfate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 235000010384 tocopherol Nutrition 0.000 description 1
- 229960001295 tocopherol Drugs 0.000 description 1
- 125000002640 tocopherol group Chemical class 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 description 1
- 125000001919 trimellityl group Chemical group C(=O)(O)C=1C=C(C(=O)*)C=CC1C(=O)O 0.000 description 1
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 150000003712 vitamin E derivatives Chemical class 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Transplantation (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (13)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0323202.2 | 2003-10-03 | ||
| GB0323202A GB0323202D0 (en) | 2003-10-03 | 2003-10-03 | Organic compounds |
| GB0323598.3 | 2003-10-08 | ||
| GB0323598A GB0323598D0 (en) | 2003-10-08 | 2003-10-08 | Organic compounds |
| GB0329852A GB0329852D0 (en) | 2003-12-23 | 2003-12-23 | Organic compounds |
| GB0329852.8 | 2003-12-23 | ||
| GB0405902A GB0405902D0 (en) | 2004-03-16 | 2004-03-16 | Organic compounds |
| GB0405902.8 | 2004-03-16 | ||
| GB0410714A GB0410714D0 (en) | 2004-05-13 | 2004-05-13 | Organic compounds |
| GB0410714.0 | 2004-05-13 | ||
| GB0419356A GB0419356D0 (en) | 2004-08-31 | 2004-08-31 | Organic compounds |
| GB0419356.1 | 2004-08-31 | ||
| PCT/EP2004/010998 WO2005034916A1 (en) | 2003-10-03 | 2004-10-01 | Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2538099A1 true CA2538099A1 (en) | 2005-04-21 |
Family
ID=34437795
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002538099A Abandoned CA2538099A1 (en) | 2003-10-03 | 2004-10-01 | Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20070036857A1 (enExample) |
| EP (1) | EP1670437A1 (enExample) |
| JP (1) | JP2007507458A (enExample) |
| AR (1) | AR045957A1 (enExample) |
| AU (1) | AU2004280078B2 (enExample) |
| BR (1) | BRPI0414864A (enExample) |
| CA (1) | CA2538099A1 (enExample) |
| MX (1) | MXPA06003646A (enExample) |
| PE (1) | PE20050755A1 (enExample) |
| TW (1) | TW200520759A (enExample) |
| WO (1) | WO2005034916A1 (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1478648B1 (en) | 2002-02-01 | 2014-04-30 | ARIAD Pharmaceuticals, Inc. | Phosphorus-containing compounds and uses thereof |
| GB0419355D0 (en) * | 2004-08-31 | 2004-09-29 | Novartis Ag | Organic compounds |
| WO2006086498A2 (en) * | 2005-02-08 | 2006-08-17 | Aspreva Pharmaceuticals Sa | Treatment of vascular, autoimmune and inflammatory diseases using low dosages of impdh inhibitors |
| GB0523659D0 (en) * | 2005-11-21 | 2005-12-28 | Novartis Ag | Organic compounds |
| KR20080094788A (ko) * | 2006-02-13 | 2008-10-24 | 노파르티스 아게 | 고복용량의 미코페놀산(엠피에이) |
| CA2669415A1 (en) * | 2006-11-14 | 2008-05-22 | Ariad Pharmaceuticals, Inc. | Solid dosage form comprising ap23573 |
| AU2008288106B2 (en) * | 2007-08-13 | 2012-03-15 | Panacea Biotec Limited | Extended release compositions comprising mycophenolate sodium and processes thereof |
| CN101969931A (zh) * | 2008-03-05 | 2011-02-09 | 万能药生物有限公司 | 包含霉酚酸的调节释放药物组合物及其方法 |
| EP2446027A1 (en) * | 2009-06-25 | 2012-05-02 | Danisco A/S | Protein |
| EA201270544A1 (ru) * | 2009-10-13 | 2012-09-28 | Тева Фармасьютикал Индастриз Лтд. | Композиции с отсроченным высвобождением |
| US10391059B2 (en) | 2009-11-11 | 2019-08-27 | Rapamycin Holdings, Inc. | Oral rapamycin nanoparticle preparations and use |
| US9283211B1 (en) | 2009-11-11 | 2016-03-15 | Rapamycin Holdings, Llc | Oral rapamycin preparation and use for stomatitis |
| EP2763663B1 (en) * | 2011-10-06 | 2017-12-27 | Novartis AG | Pharmaceutical compositions comprising 40-o-(2-hydroxy)ethyl-rapamycin |
| JP2015533174A (ja) * | 2012-10-11 | 2015-11-19 | セラヴィダ，インコーポレイテッド | ピロカルピンの医薬製剤 |
| TW201503912A (zh) | 2013-03-19 | 2015-02-01 | Novartis Ag | 包含癌莫事（ｅｖｅｒｏｌｉｍｕｓ）之醫藥組合物 |
| WO2014167442A1 (en) * | 2013-03-26 | 2014-10-16 | Wockhardt Limited | Pharmaceutical compositions comprising mycophenolic acid or salts thereof |
| US9700544B2 (en) | 2013-12-31 | 2017-07-11 | Neal K Vail | Oral rapamycin nanoparticle preparations |
| HUP1400075A2 (hu) | 2014-02-14 | 2015-08-28 | Druggability Technologies Ip Holdco Jersey Ltd | Sirolimus és származékainak komplexei, elõállítása és gyógyszerészeti kompozíciói |
| MA40982A (fr) * | 2014-11-19 | 2017-09-26 | Biogen Ma Inc | Formulation de bille pharmaceutique comprenant du fumarate de diméthyle |
| US10576076B2 (en) | 2015-05-20 | 2020-03-03 | Novartis Ag | Pharmaceutical combination of everolimus with dactolisib |
| JP2020500930A (ja) | 2016-11-23 | 2020-01-16 | ノバルティス アーゲー | エベロリムス、ダクトリシブまたは両方で免疫応答を増強する方法 |
| MX2019010829A (es) * | 2017-03-13 | 2020-02-05 | Okava Pharmaceuticals Inc | Metodos y composiciones para suministrar agentes activos de acido micofenolico a mamiferos no humanos. |
| WO2019157516A1 (en) | 2018-02-12 | 2019-08-15 | resTORbio, Inc. | Combination therapies |
| US11446055B1 (en) | 2018-10-18 | 2022-09-20 | Lumoptik, Inc. | Light assisted needle placement system and method |
| US20250282721A9 (en) * | 2021-12-23 | 2025-09-11 | Gencaps Sàrl | Drug delivery system comprising monomethyl fumarate |
| WO2023224914A1 (en) * | 2022-05-16 | 2023-11-23 | Mayo Foundation For Medical Education And Research | Assessing and treating caveolinopathy diseases |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2086642C (en) * | 1992-01-09 | 2004-06-15 | Randall E. Morris | Method of treating hyperproliferative vascular disease |
| US5516781A (en) * | 1992-01-09 | 1996-05-14 | American Home Products Corporation | Method of treating restenosis with rapamycin |
| US5283257A (en) * | 1992-07-10 | 1994-02-01 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
| PL177323B1 (pl) * | 1993-10-01 | 1999-10-29 | Syntex Inc | Kompozycja farmaceutyczna zawierająca mykofenolan mofetylu lub kwas mykofenolowy i sposób wytwarzania kompozycji farmaceutycznej zawierającej mykofenolan mofetylu lub kwas mykofenolowy |
| ID18663A (id) * | 1996-04-12 | 1998-04-30 | Novartis Ag | Komposisi farmasi berlapis enterik |
| CN1233169A (zh) * | 1996-10-14 | 1999-10-27 | 弗·哈夫曼-拉罗切有限公司 | 一种粉末状制剂的制备工艺 |
| US6890546B2 (en) * | 1998-09-24 | 2005-05-10 | Abbott Laboratories | Medical devices containing rapamycin analogs |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| WO2000067773A2 (en) * | 1999-05-10 | 2000-11-16 | Novartis Ag | Combinations of immunosupressive agents for the treatment or prevention of graft rejections |
| US6565882B2 (en) * | 2000-02-24 | 2003-05-20 | Advancis Pharmaceutical Corp | Antibiotic composition with inhibitor |
| US20030054042A1 (en) * | 2001-09-14 | 2003-03-20 | Elaine Liversidge | Stabilization of chemical compounds using nanoparticulate formulations |
| GB0124953D0 (en) * | 2001-10-17 | 2001-12-05 | Novartis Ag | Organic Compounds |
| JP2005514411A (ja) * | 2002-01-10 | 2005-05-19 | ノバルティス アクチエンゲゼルシャフト | ラパマイシンおよびその誘導体を含む血管疾患の予防および処置用薬剤送達システム |
| SI1539157T1 (sl) * | 2002-09-18 | 2013-11-29 | Trustees Of The University Of Pennsylvania | Rapamicin za uporabo pri inhibiciji ali preprečevanju horoidalne neovaskularizacije |
| CA2500908A1 (en) * | 2002-10-04 | 2004-04-22 | Elan Pharma International Limited | Gamma irradiation of solid nanoparticulate active agents |
| GB0301259D0 (en) * | 2003-01-20 | 2003-02-19 | Novartis Ag | Organic compounds |
| GB0307553D0 (en) * | 2003-04-01 | 2003-05-07 | Novartis Ag | Organic compounds |
-
2004
- 2004-09-30 AR ARP040103556A patent/AR045957A1/es unknown
- 2004-10-01 AU AU2004280078A patent/AU2004280078B2/en not_active Ceased
- 2004-10-01 BR BRPI0414864-9A patent/BRPI0414864A/pt not_active IP Right Cessation
- 2004-10-01 PE PE2004000963A patent/PE20050755A1/es not_active Application Discontinuation
- 2004-10-01 JP JP2006530072A patent/JP2007507458A/ja active Pending
- 2004-10-01 US US10/570,752 patent/US20070036857A1/en not_active Abandoned
- 2004-10-01 TW TW093129854A patent/TW200520759A/zh unknown
- 2004-10-01 WO PCT/EP2004/010998 patent/WO2005034916A1/en not_active Ceased
- 2004-10-01 EP EP04765757A patent/EP1670437A1/en not_active Withdrawn
- 2004-10-01 MX MXPA06003646A patent/MXPA06003646A/es not_active Application Discontinuation
- 2004-10-01 CA CA002538099A patent/CA2538099A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1670437A1 (en) | 2006-06-21 |
| BRPI0414864A (pt) | 2006-11-28 |
| JP2007507458A (ja) | 2007-03-29 |
| MXPA06003646A (es) | 2006-06-05 |
| AU2004280078A1 (en) | 2005-04-21 |
| WO2005034916A1 (en) | 2005-04-21 |
| TW200520759A (en) | 2005-07-01 |
| US20070036857A1 (en) | 2007-02-15 |
| AR045957A1 (es) | 2005-11-16 |
| PE20050755A1 (es) | 2005-11-28 |
| AU2004280078B2 (en) | 2008-08-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2004280078B2 (en) | Pharmaceutical multiparticulate composition comprising mycophenolic acid or mycophenolate sodium and combination with rapamycin | |
| EP1438040B1 (en) | Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt | |
| DK2210605T3 (en) | Daily single dose doses of trospium. | |
| US20080206322A1 (en) | Pharmaceutical Multiparticulate Composit Ion Comprising Mycophenolic Acid or Myco Phenolate Sodium and Combination Compositions with Rapamycin | |
| AU2002338897A1 (en) | Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt | |
| AU2008288106B2 (en) | Extended release compositions comprising mycophenolate sodium and processes thereof | |
| AU731693B2 (en) | Drug formulation having controlled release of active compound | |
| CA2578375A1 (en) | Vaccine immunotherapy for immune suppressed patients | |
| HK1067861B (en) | Pharmaceutical compositions comprising mycophenolic acid or mycophenolate salt |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |