NZ569700A - Polymer formulations of CETP inhibitors - Google Patents
Polymer formulations of CETP inhibitorsInfo
- Publication number
- NZ569700A NZ569700A NZ569700A NZ56970007A NZ569700A NZ 569700 A NZ569700 A NZ 569700A NZ 569700 A NZ569700 A NZ 569700A NZ 56970007 A NZ56970007 A NZ 56970007A NZ 569700 A NZ569700 A NZ 569700A
- Authority
- NZ
- New Zealand
- Prior art keywords
- cellulose acetate
- pharmaceutical composition
- compound
- phthalate
- concentration
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 131
- 229920000642 polymer Polymers 0.000 title claims abstract description 102
- 238000009472 formulation Methods 0.000 title description 65
- 239000003354 cholesterol ester transfer protein inhibitor Substances 0.000 title description 30
- 229920002301 cellulose acetate Polymers 0.000 claims abstract description 37
- 239000004094 surface-active agent Substances 0.000 claims abstract description 31
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims abstract description 26
- -1 sorbitan fatty acid esters Chemical class 0.000 claims abstract description 26
- AOBORMOPSGHCAX-UHFFFAOYSA-N Tocophersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 229920000623 Cellulose acetate phthalate Polymers 0.000 claims abstract description 19
- 229940081734 cellulose acetate phthalate Drugs 0.000 claims abstract description 19
- GAMPNQJDUFQVQO-UHFFFAOYSA-N acetic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O GAMPNQJDUFQVQO-UHFFFAOYSA-N 0.000 claims abstract description 18
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims abstract description 17
- ZUAAPNNKRHMPKG-UHFFFAOYSA-N acetic acid;butanedioic acid;methanol;propane-1,2-diol Chemical compound OC.CC(O)=O.CC(O)CO.OC(=O)CCC(O)=O ZUAAPNNKRHMPKG-UHFFFAOYSA-N 0.000 claims abstract description 17
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims abstract description 17
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims abstract description 16
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims abstract description 16
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims abstract description 14
- 125000005591 trimellitate group Chemical group 0.000 claims abstract description 14
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000004359 castor oil Substances 0.000 claims abstract description 8
- WZNRVWBKYDHTKI-UHFFFAOYSA-N cellulose, acetate 1,2,4-benzenetricarboxylate Chemical compound OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.OC1C(O)C(O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.CC(=O)OCC1OC(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(COC(C)=O)O1.OC(=O)C1=CC(C(=O)O)=CC=C1C(=O)OCC1C(OC2C(C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(OC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)C(COC(=O)C=3C(=CC(=CC=3)C(O)=O)C(O)=O)O2)OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)C(OC(=O)C=2C(=CC(=CC=2)C(O)=O)C(O)=O)O1 WZNRVWBKYDHTKI-UHFFFAOYSA-N 0.000 claims abstract description 8
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 8
- 239000000194 fatty acid Substances 0.000 claims abstract description 8
- 229930195729 fatty acid Natural products 0.000 claims abstract description 8
- 229920000609 methyl cellulose Polymers 0.000 claims abstract description 8
- 239000001923 methylcellulose Substances 0.000 claims abstract description 8
- 235000010981 methylcellulose Nutrition 0.000 claims abstract description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims abstract description 7
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims abstract description 7
- ZNPLZHBZUSCANM-UHFFFAOYSA-N acetic acid;benzene-1,3-dicarboxylic acid Chemical compound CC(O)=O.OC(=O)C1=CC=CC(C(O)=O)=C1 ZNPLZHBZUSCANM-UHFFFAOYSA-N 0.000 claims abstract description 6
- FMTQGBMMIVVKSN-UHFFFAOYSA-N acetic acid;terephthalic acid Chemical compound CC(O)=O.OC(=O)C1=CC=C(C(O)=O)C=C1 FMTQGBMMIVVKSN-UHFFFAOYSA-N 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 108010023302 HDL Cholesterol Proteins 0.000 claims abstract description 5
- 229920001214 Polysorbate 60 Polymers 0.000 claims abstract description 4
- KEWSCDNULKOKTG-UHFFFAOYSA-N 4-cyano-4-ethylsulfanylcarbothioylsulfanylpentanoic acid Chemical compound CCSC(=S)SC(C)(C#N)CCC(O)=O KEWSCDNULKOKTG-UHFFFAOYSA-N 0.000 claims abstract 3
- 102100037637 Cholesteryl ester transfer protein Human genes 0.000 claims abstract 3
- 101000880514 Homo sapiens Cholesteryl ester transfer protein Proteins 0.000 claims abstract 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract 3
- 229940081735 acetylcellulose Drugs 0.000 claims description 34
- 239000003814 drug Substances 0.000 claims description 32
- 150000001875 compounds Chemical class 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 19
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 18
- 239000000945 filler Substances 0.000 claims description 16
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 14
- 238000001694 spray drying Methods 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 13
- 238000009474 hot melt extrusion Methods 0.000 claims description 13
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 13
- 229920001531 copovidone Polymers 0.000 claims description 12
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 11
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 10
- 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 claims description 9
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 9
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 9
- 235000019359 magnesium stearate Nutrition 0.000 claims description 9
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 8
- 239000007884 disintegrant Substances 0.000 claims description 8
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 8
- 239000011118 polyvinyl acetate Substances 0.000 claims description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 8
- 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 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 7
- 239000008101 lactose Substances 0.000 claims description 7
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 7
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 7
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 239000000314 lubricant Substances 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000002736 nonionic surfactant Substances 0.000 claims description 3
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group 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 1
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical compound O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 abstract description 11
- 125000001424 substituent group Chemical group 0.000 abstract description 11
- 229920001577 copolymer Polymers 0.000 abstract description 6
- 239000000243 solution Substances 0.000 description 36
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
- 229940079593 drug Drugs 0.000 description 29
- 239000007787 solid Substances 0.000 description 28
- 238000000034 method Methods 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 23
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000007921 spray Substances 0.000 description 18
- 239000006185 dispersion Substances 0.000 description 17
- 229940125881 cholesteryl ester transfer protein inhibitor Drugs 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 230000008569 process Effects 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 13
- 239000002245 particle Substances 0.000 description 13
- 238000012545 processing Methods 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 11
- 229910052757 nitrogen Inorganic materials 0.000 description 11
- 235000010980 cellulose Nutrition 0.000 description 10
- 229920002678 cellulose Polymers 0.000 description 10
- 239000001913 cellulose Substances 0.000 description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
- 239000010410 layer Substances 0.000 description 10
- 238000002156 mixing Methods 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 239000003826 tablet Substances 0.000 description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 description 8
- 238000001125 extrusion Methods 0.000 description 8
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- 230000001965 increasing effect Effects 0.000 description 8
- 239000002002 slurry Substances 0.000 description 8
- 238000008214 LDL Cholesterol Methods 0.000 description 7
- 208000029078 coronary artery disease Diseases 0.000 description 7
- 239000007789 gas Substances 0.000 description 7
- 239000004615 ingredient Substances 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 7
- 108010061846 Cholesterol Ester Transfer Proteins Proteins 0.000 description 6
- 102000012336 Cholesterol Ester Transfer Proteins Human genes 0.000 description 6
- 108010010234 HDL Lipoproteins Proteins 0.000 description 6
- 229920003083 Kollidon® VA64 Polymers 0.000 description 6
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 6
- IYKJEILNJZQJPU-UHFFFAOYSA-N acetic acid;butanedioic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O IYKJEILNJZQJPU-UHFFFAOYSA-N 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 201000001320 Atherosclerosis Diseases 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 235000012000 cholesterol Nutrition 0.000 description 5
- 230000002496 gastric effect Effects 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 229960001375 lactose Drugs 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 5
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 4
- 239000001856 Ethyl cellulose Substances 0.000 description 4
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- 241000282560 Macaca mulatta Species 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
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- 239000002775 capsule Substances 0.000 description 4
- 229920006218 cellulose propionate Polymers 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000002425 crystallisation Methods 0.000 description 4
- 230000008025 crystallization Effects 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 4
- 229920000053 polysorbate 80 Polymers 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 238000006467 substitution reaction Methods 0.000 description 4
- CGMMPMYKMDITEA-UHFFFAOYSA-N 2-ethylbenzoic acid Chemical compound CCC1=CC=CC=C1C(O)=O CGMMPMYKMDITEA-UHFFFAOYSA-N 0.000 description 3
- WSVLPVUVIUVCRA-KPKNDVKVSA-N Alpha-lactose monohydrate Chemical compound O.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 WSVLPVUVIUVCRA-KPKNDVKVSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 229910019142 PO4 Inorganic materials 0.000 description 3
- 208000018262 Peripheral vascular disease Diseases 0.000 description 3
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- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 3
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- PLEULVPCZZDBNB-UHFFFAOYSA-N acetic acid;butanedioic acid;phthalic acid Chemical compound CC(O)=O.OC(=O)CCC(O)=O.OC(=O)C1=CC=CC=C1C(O)=O PLEULVPCZZDBNB-UHFFFAOYSA-N 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
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- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 description 3
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
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- TYRGLVWXHJRKMT-QMMMGPOBSA-N n-benzyloxycarbonyl-l-serine-betalactone Chemical compound OC(=O)[C@H](C)NC(=O)OCC1=CC=CC=C1 TYRGLVWXHJRKMT-QMMMGPOBSA-N 0.000 description 3
- QUANRIQJNFHVEU-UHFFFAOYSA-N oxirane;propane-1,2,3-triol Chemical compound C1CO1.OCC(O)CO QUANRIQJNFHVEU-UHFFFAOYSA-N 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
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- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 3
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 2
- ZNNQGSGPVUYWOS-UHFFFAOYSA-N 2-(3-hydroxypropoxy)benzoic acid Chemical compound OCCCOC1=CC=CC=C1C(O)=O ZNNQGSGPVUYWOS-UHFFFAOYSA-N 0.000 description 2
- XDZMPRGFOOFSBL-UHFFFAOYSA-N 2-ethoxybenzoic acid Chemical group CCOC1=CC=CC=C1C(O)=O XDZMPRGFOOFSBL-UHFFFAOYSA-N 0.000 description 2
- OEXIDSNKGPWFGB-UHFFFAOYSA-N 2-ethyl-3-(3-hydroxypropyl)benzoic acid Chemical compound CCC1=C(CCCO)C=CC=C1C(O)=O OEXIDSNKGPWFGB-UHFFFAOYSA-N 0.000 description 2
- RESGCFMULOVHHB-UHFFFAOYSA-N 2-ethylpyridine-3-carboxylic acid Chemical compound CCC1=NC=CC=C1C(O)=O RESGCFMULOVHHB-UHFFFAOYSA-N 0.000 description 2
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- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- VCNSALVCAYTUFA-UHFFFAOYSA-M sodium;dodecan-5-yl sulfate Chemical compound [Na+].CCCCCCCC(OS([O-])(=O)=O)CCCC VCNSALVCAYTUFA-UHFFFAOYSA-M 0.000 description 1
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Classifications
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
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- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
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- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
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- A61K9/2022—Organic macromolecular compounds
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
Landscapes
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- Veterinary Medicine (AREA)
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- Animal Behavior & Ethology (AREA)
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- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Steroid Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US77178206P | 2006-02-09 | 2006-02-09 | |
| PCT/US2007/003799 WO2007092642A2 (en) | 2006-02-09 | 2007-02-09 | Polymer formulations of cetp inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ569700A true NZ569700A (en) | 2011-09-30 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ569700A NZ569700A (en) | 2006-02-09 | 2007-02-09 | Polymer formulations of CETP inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US8030359B2 (enExample) |
| EP (1) | EP1983966B1 (enExample) |
| JP (2) | JP5773560B2 (enExample) |
| KR (1) | KR101418267B1 (enExample) |
| CN (2) | CN101378731B (enExample) |
| AU (1) | AU2007212197B2 (enExample) |
| BR (1) | BRPI0707584A2 (enExample) |
| CA (1) | CA2641451C (enExample) |
| IL (1) | IL192977A (enExample) |
| NO (1) | NO341326B1 (enExample) |
| NZ (1) | NZ569700A (enExample) |
| RU (1) | RU2457841C2 (enExample) |
| WO (1) | WO2007092642A2 (enExample) |
| ZA (1) | ZA200805854B (enExample) |
Families Citing this family (26)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004085996A2 (en) | 2003-03-20 | 2004-10-07 | Albert Einstein College Of Medicine Of Yeshiva University | Biomarkers for longevity and disease and uses thereof |
| US9040558B2 (en) | 2004-12-31 | 2015-05-26 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| US8604055B2 (en) | 2004-12-31 | 2013-12-10 | Dr. Reddy's Laboratories Ltd. | Substituted benzylamino quinolines as cholesterol ester-transfer protein inhibitors |
| US20090143423A1 (en) * | 2007-10-19 | 2009-06-04 | Abbott Gmbh & Co. Kg | Solid dispersion product containing n-aryl urea-based compound |
| WO2009108720A2 (en) | 2008-02-25 | 2009-09-03 | Amira Pharmaceuticals, Inc. | Antagonists of prostaglandin d2 receptors |
| AR071375A1 (es) * | 2008-04-22 | 2010-06-16 | Solvay Pharm Gmbh | Formulaciones para ingredientes farmaceuticos activos de permeabilidad deficiente, proceso de preparacion y producto |
| KR101944124B1 (ko) | 2010-11-24 | 2019-01-30 | 멜린타 서브시디어리 코프. | 약학 조성물 |
| US9867811B2 (en) * | 2011-07-08 | 2018-01-16 | Novartis Ag | Method of treating atherosclerosis in high triglyceride subjects |
| US9199967B2 (en) | 2011-08-18 | 2015-12-01 | Dr. Reddy's Laboratories Ltd. | Substituted heterocyclic amine compounds as cholestryl ester-transfer protein (CETP) inhibitors |
| IN2014CN02290A (enExample) | 2011-09-27 | 2015-06-19 | Reddys Lab Ltd Dr | |
| RU2759837C2 (ru) | 2012-05-31 | 2021-11-18 | Мерк Шарп И Доум Корп. | Составы твердых дозированных лекарственных форм антагониста орексинового рецептора |
| JP6235584B2 (ja) * | 2012-07-17 | 2017-11-22 | ダウ グローバル テクノロジーズ エルエルシー | 高置換ヒドロキシアルキルメチルセルロースを含む固体分散体 |
| JP6301339B2 (ja) * | 2012-09-27 | 2018-03-28 | ビーエーエスエフ ソシエタス・ヨーロピアＢａｓｆ Ｓｅ | 少なくとも１種の水溶性ビタミンｅ誘導体および少なくとも１種の親水性ポリマーを含む、保存において安定な無塵の均質な粒子製剤 |
| CA2891502A1 (en) | 2012-11-19 | 2014-05-22 | Dr. Reddy's Laboratories Ltd. | Pharmaceutical compositions of cetp inhibitors |
| WO2015077273A1 (en) * | 2013-11-22 | 2015-05-28 | Merck Sharp & Dohme Corp. | Composition of a non-nucleoside reverse transcriptase inhibitor |
| US12168004B2 (en) | 2014-02-05 | 2024-12-17 | Merck Sharp & Dohme Llc | Treatment of migraine |
| KR20230107902A (ko) * | 2014-02-05 | 2023-07-18 | 머크 샤프 앤드 돔 엘엘씨 | Cgrp-활성 화합물에 대한 정제 제제 |
| JPWO2016084949A1 (ja) * | 2014-11-28 | 2017-09-07 | 興和株式会社 | 医薬 |
| JOP20180092A1 (ar) | 2017-10-13 | 2019-04-13 | Gilead Sciences Inc | مثبطات hiv بروتياز |
| US12383545B1 (en) | 2018-06-08 | 2025-08-12 | Allergan Pharmaceuticals International Limited | Treatment of migraine |
| CN114617968B (zh) * | 2019-04-09 | 2023-10-03 | 北京五和博澳药业股份有限公司 | 黄酮多酚类药物自乳化组合物、其制备方法、药物组合物及用途 |
| HRP20241585T1 (hr) * | 2019-04-12 | 2025-01-31 | Oblita Therapeutics Bvba | Fototaloženje metalnih oksida za elektrokromne uređaje |
| TW202104210A (zh) | 2019-04-17 | 2021-02-01 | 美商基利科學股份有限公司 | Hiv蛋白酶抑制劑 |
| AU2021319090A1 (en) | 2020-07-29 | 2023-03-02 | Allergan Pharmaceuticals International Limited | Treatment of migraine |
| WO2022140537A1 (en) | 2020-12-22 | 2022-06-30 | Allergan Pharmaceuticals International Limited | Treatment of migraine |
| JP2024533756A (ja) | 2021-09-27 | 2024-09-12 | アラガン ファーマスーティカルズ インターナショナル リミテッド | アトゲパントを含む片頭痛の併用療法 |
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| US7115279B2 (en) * | 2000-08-03 | 2006-10-03 | Curatolo William J | Pharmaceutical compositions of cholesteryl ester transfer protein inhibitors |
| US6627767B2 (en) * | 2000-08-29 | 2003-09-30 | Abbott Laboratories | Amino(oxo) acetic acid protein tyrosine phosphatase inhibitors |
| WO2003000294A1 (en) | 2001-06-22 | 2003-01-03 | Pfizer Products Inc. | Pharmaceutical compositions containing a solid dispersion of a poorly-soluble drug in a matrix and a solubility-enhancing polymer |
| EP1269994A3 (en) | 2001-06-22 | 2003-02-12 | Pfizer Products Inc. | Pharmaceutical compositions comprising drug and concentration-enhancing polymers |
| RS51865B (sr) | 2002-01-29 | 2012-02-29 | Laboratoires Serono Sa. | Supstituisani derivati metilen amida kao modulatori protein tirozin fosfataze (ptp) |
| EP1474144B1 (en) * | 2002-02-01 | 2008-08-06 | Pfizer Products Inc. | Controlled release pharmaceutical dosage forms of a cholesteryl ester transfer protein inhibitor |
| EP1469830A2 (en) | 2002-02-01 | 2004-10-27 | Pfizer Products Inc. | Method for making homogeneous spray-dried solid amorphous drug dispersions using pressure nozzles |
| SK2332004A3 (en) * | 2002-08-30 | 2004-12-01 | Japan Tobacco Inc | Dibenzylamine compound and medicinal use thereof |
| ATE534381T1 (de) | 2003-03-17 | 2011-12-15 | Japan Tobacco Inc | Pharmazeutische cetp-inhibitor-zusammensetzungen |
| US20070043079A1 (en) | 2003-04-18 | 2007-02-22 | Hiromu Habashita | Heterocyclic compound containing nitrogen atom and use thereof |
| DOP2005000123A (es) * | 2004-07-02 | 2011-07-15 | Merck Sharp & Dohme | Inhibidores de cetp |
| FR2875409B1 (fr) * | 2004-09-17 | 2010-05-07 | Sanofi Aventis | Composition pharmaceutique comprenant une dispersion solide a matrice polymere comprenant une phase continue de polydextrose et une phase continue d'un polymere autre que du polydextrose |
| AU2006265975B2 (en) * | 2005-07-01 | 2011-12-15 | Merck Sharp & Dohme Corp. | Process for synthesizing a CETP inhibitor |
| ATE516016T1 (de) | 2005-12-05 | 2011-07-15 | Merck Sharp & Dohme | Selbstemulgierende formulierungen von cetp- hemmern |
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| CN101378731A (zh) | 2009-03-04 |
| CN101378731B (zh) | 2014-03-05 |
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| RU2008136198A (ru) | 2010-03-20 |
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| ZA200805854B (en) | 2009-10-28 |
| EP1983966B1 (en) | 2013-06-26 |
| EP1983966A2 (en) | 2008-10-29 |
| US20100227903A1 (en) | 2010-09-09 |
| US8030359B2 (en) | 2011-10-04 |
| KR20080108420A (ko) | 2008-12-15 |
| KR101418267B1 (ko) | 2014-07-11 |
| NO20083821L (no) | 2008-09-30 |
| CA2641451A1 (en) | 2007-08-16 |
| WO2007092642A2 (en) | 2007-08-16 |
| CN103735515A (zh) | 2014-04-23 |
| JP2009526075A (ja) | 2009-07-16 |
| NO341326B1 (no) | 2017-10-16 |
| WO2007092642A3 (en) | 2007-10-04 |
| BRPI0707584A2 (pt) | 2011-05-10 |
| JP2013067635A (ja) | 2013-04-18 |
| CA2641451C (en) | 2012-10-02 |
| JP5773560B2 (ja) | 2015-09-02 |
| JP5648038B2 (ja) | 2015-01-07 |
| RU2457841C2 (ru) | 2012-08-10 |
| IL192977A (en) | 2011-01-31 |
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