NO325005B1 - Krystallinske former av lopinavir, farmasoytiske sammensetninger omfattende disse og deres anvendelse - Google Patents
Krystallinske former av lopinavir, farmasoytiske sammensetninger omfattende disse og deres anvendelse Download PDFInfo
- Publication number
- NO325005B1 NO325005B1 NO20024679A NO20024679A NO325005B1 NO 325005 B1 NO325005 B1 NO 325005B1 NO 20024679 A NO20024679 A NO 20024679A NO 20024679 A NO20024679 A NO 20024679A NO 325005 B1 NO325005 B1 NO 325005B1
- Authority
- NO
- Norway
- Prior art keywords
- lopinavir
- type
- solvated
- peak
- crystal form
- Prior art date
Links
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 title claims description 397
- 229960004525 lopinavir Drugs 0.000 title claims description 397
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 15
- 239000007790 solid phase Substances 0.000 claims description 108
- 238000002329 infrared spectrum Methods 0.000 claims description 56
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 33
- 238000002156 mixing Methods 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 12
- 208000031886 HIV Infections Diseases 0.000 claims description 7
- 208000037357 HIV infectious disease Diseases 0.000 claims description 7
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 2
- 239000004615 ingredient Substances 0.000 claims 2
- 239000007904 elastic gelatin capsule Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 description 272
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 160
- 235000019439 ethyl acetate Nutrition 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 39
- 239000000243 solution Substances 0.000 description 37
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 34
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- 239000000047 product Substances 0.000 description 30
- 238000002360 preparation method Methods 0.000 description 27
- 239000002904 solvent Substances 0.000 description 27
- 238000000892 gravimetry Methods 0.000 description 18
- 239000000523 sample Substances 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
- 238000004476 mid-IR spectroscopy Methods 0.000 description 17
- 239000000203 mixture Substances 0.000 description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 13
- -1 amorphous Chemical compound 0.000 description 11
- 238000002425 crystallisation Methods 0.000 description 11
- 230000008025 crystallization Effects 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- 239000012453 solvate Substances 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 239000002244 precipitate Substances 0.000 description 9
- 239000002002 slurry Substances 0.000 description 8
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 6
- 239000006260 foam Substances 0.000 description 6
- 239000011521 glass Substances 0.000 description 6
- 229960000311 ritonavir Drugs 0.000 description 6
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 6
- 238000001228 spectrum Methods 0.000 description 6
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 5
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 5
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 5
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 5
- 239000005642 Oleic acid Substances 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 5
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
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- 239000000725 suspension Substances 0.000 description 5
- 238000004566 IR spectroscopy Methods 0.000 description 4
- 238000002441 X-ray diffraction Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 239000012047 saturated solution Substances 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000000113 differential scanning calorimetry Methods 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 description 3
- 238000001757 thermogravimetry curve Methods 0.000 description 3
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 2
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 2
- XHLHPRDBBAGVEG-UHFFFAOYSA-N 1-tetralone Chemical compound C1=CC=C2C(=O)CCCC2=C1 XHLHPRDBBAGVEG-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 2
- 108010010369 HIV Protease Proteins 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- URLKBWYHVLBVBO-UHFFFAOYSA-N Para-Xylene Chemical group CC1=CC=C(C)C=C1 URLKBWYHVLBVBO-UHFFFAOYSA-N 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000012296 anti-solvent Substances 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N butyl acetate Chemical compound CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 239000004030 hiv protease inhibitor Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 238000003760 magnetic stirring Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 239000003495 polar organic solvent Substances 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 238000007614 solvation Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- FCGXLCNBWYIEAA-UHFFFAOYSA-N 1,3-benzothiazol-6-ylmethanamine Chemical compound NCC1=CC=C2N=CSC2=C1 FCGXLCNBWYIEAA-UHFFFAOYSA-N 0.000 description 1
- FIDGQQIVMWAIAD-UHFFFAOYSA-N 2,2,4,4-tetramethyloxolane Chemical compound CC1(C)COC(C)(C)C1 FIDGQQIVMWAIAD-UHFFFAOYSA-N 0.000 description 1
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 1
- MSXVEPNJUHWQHW-UHFFFAOYSA-N 2-methylbutan-2-ol Chemical compound CCC(C)(C)O MSXVEPNJUHWQHW-UHFFFAOYSA-N 0.000 description 1
- XKIRHOWVQWCYBT-UHFFFAOYSA-N 3-ethylpentan-3-ol Chemical compound CCC(O)(CC)CC XKIRHOWVQWCYBT-UHFFFAOYSA-N 0.000 description 1
- 229940122440 HIV protease inhibitor Drugs 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000005004 MAS NMR spectroscopy Methods 0.000 description 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229940095564 anhydrous calcium sulfate Drugs 0.000 description 1
- 229910001632 barium fluoride Inorganic materials 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 1
- 229910001634 calcium fluoride Inorganic materials 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 239000001175 calcium sulphate Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004320 controlled atmosphere Methods 0.000 description 1
- 239000002178 crystalline material Substances 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052732 germanium Inorganic materials 0.000 description 1
- GNPVGFCGXDBREM-UHFFFAOYSA-N germanium atom Chemical compound [Ge] GNPVGFCGXDBREM-UHFFFAOYSA-N 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000000887 hydrating effect Effects 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- LWXUXIDLCWPHIW-GSDHBNRESA-N n-[(2s,3s,5s)-5-amino-3-hydroxy-1,6-diphenylhexan-2-yl]-2-(2,6-dimethylphenoxy)acetamide Chemical compound CC1=CC=CC(C)=C1OCC(=O)N[C@H]([C@@H](O)C[C@@H](N)CC=1C=CC=CC=1)CC1=CC=CC=C1 LWXUXIDLCWPHIW-GSDHBNRESA-N 0.000 description 1
- 238000001208 nuclear magnetic resonance pulse sequence Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000002985 plastic film Substances 0.000 description 1
- 229920006255 plastic film Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N silicon dioxide Inorganic materials O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 238000010583 slow cooling Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine 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 directly attached in position 2
- C07D239/10—Oxygen or sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Virology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Communicable Diseases (AREA)
- Molecular Biology (AREA)
- AIDS & HIV (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US53825700A | 2000-03-30 | 2000-03-30 | |
| US09/793,536 US6608198B2 (en) | 2000-03-30 | 2001-02-27 | Crystalline pharmaceutical |
| PCT/US2001/009112 WO2001074787A2 (en) | 2000-03-30 | 2001-03-21 | Crystalline pharmaceutical |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20024679D0 NO20024679D0 (no) | 2002-09-30 |
| NO20024679L NO20024679L (no) | 2002-09-30 |
| NO325005B1 true NO325005B1 (no) | 2008-01-14 |
Family
ID=27065762
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20024679A NO325005B1 (no) | 2000-03-30 | 2002-09-30 | Krystallinske former av lopinavir, farmasoytiske sammensetninger omfattende disse og deres anvendelse |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP1268442A2 (bg) |
| JP (1) | JP2003529592A (bg) |
| KR (1) | KR100773258B1 (bg) |
| CN (2) | CN101066952A (bg) |
| AR (2) | AR033360A1 (bg) |
| AU (3) | AU5092001A (bg) |
| BG (1) | BG107165A (bg) |
| BR (1) | BR0109433A (bg) |
| CA (1) | CA2403635A1 (bg) |
| CZ (1) | CZ20023529A3 (bg) |
| HU (1) | HUP0302675A3 (bg) |
| IL (1) | IL151551A0 (bg) |
| MX (1) | MXPA02009559A (bg) |
| MY (1) | MY128296A (bg) |
| NO (1) | NO325005B1 (bg) |
| NZ (1) | NZ521183A (bg) |
| PE (1) | PE20011232A1 (bg) |
| PL (1) | PL359727A1 (bg) |
| SA (2) | SA06270303B1 (bg) |
| SK (1) | SK14832002A3 (bg) |
| TW (1) | TWI284640B (bg) |
| WO (1) | WO2001074787A2 (bg) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6608198B2 (en) | 2000-03-30 | 2003-08-19 | Abbott Laboratories | Crystalline pharmaceutical |
| US8025899B2 (en) | 2003-08-28 | 2011-09-27 | Abbott Laboratories | Solid pharmaceutical dosage form |
| US8445506B2 (en) | 2009-02-06 | 2013-05-21 | Hetero Research Foundation | Polymorphs of lopinavir |
| US8637449B2 (en) * | 2009-08-27 | 2014-01-28 | Merck Sharp & Dohme Corp. | Processes for preparing protease inhibitors of hepatitis C virus |
| CN112830899A (zh) * | 2021-01-18 | 2021-05-25 | 合肥华方医药科技有限公司 | 一种洛匹那韦新晶型及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5914332A (en) * | 1995-12-13 | 1999-06-22 | Abbott Laboratories | Retroviral protease inhibiting compounds |
| WO1998057648A1 (en) * | 1997-06-16 | 1998-12-23 | Vertex Pharmaceuticals Incorporated | Methods of increasing the bioavailability of stable crystal polymorphs of a compound |
-
2001
- 2001-03-07 MY MYPI20011034A patent/MY128296A/en unknown
- 2001-03-21 WO PCT/US2001/009112 patent/WO2001074787A2/en active IP Right Grant
- 2001-03-21 JP JP2001572482A patent/JP2003529592A/ja active Pending
- 2001-03-21 AU AU5092001A patent/AU5092001A/xx active Pending
- 2001-03-21 AU AU2001250920A patent/AU2001250920B2/en not_active Revoked
- 2001-03-21 KR KR1020027012849A patent/KR100773258B1/ko active IP Right Grant
- 2001-03-21 CN CNA2007101123988A patent/CN101066952A/zh active Pending
- 2001-03-21 CA CA002403635A patent/CA2403635A1/en not_active Abandoned
- 2001-03-21 SK SK1483-2002A patent/SK14832002A3/sk not_active Application Discontinuation
- 2001-03-21 BR BR0109433-5A patent/BR0109433A/pt not_active Application Discontinuation
- 2001-03-21 HU HU0302675A patent/HUP0302675A3/hu unknown
- 2001-03-21 NZ NZ521183A patent/NZ521183A/en not_active IP Right Cessation
- 2001-03-21 EP EP01924250A patent/EP1268442A2/en not_active Withdrawn
- 2001-03-21 MX MXPA02009559A patent/MXPA02009559A/es active IP Right Grant
- 2001-03-21 IL IL15155101A patent/IL151551A0/xx unknown
- 2001-03-21 CZ CZ20023529A patent/CZ20023529A3/cs unknown
- 2001-03-21 CN CNB018076882A patent/CN1330639C/zh not_active Expired - Lifetime
- 2001-03-21 PL PL35972701A patent/PL359727A1/xx not_active Application Discontinuation
- 2001-03-29 AR ARP010101522A patent/AR033360A1/es not_active Application Discontinuation
- 2001-03-30 PE PE2001000299A patent/PE20011232A1/es not_active Application Discontinuation
- 2001-05-02 TW TW090107717A patent/TWI284640B/zh active
- 2001-08-07 SA SA06270303A patent/SA06270303B1/ar unknown
- 2001-08-07 SA SA01220270A patent/SA01220270B1/ar unknown
-
2002
- 2002-09-30 NO NO20024679A patent/NO325005B1/no not_active Application Discontinuation
- 2002-10-03 BG BG107165A patent/BG107165A/bg unknown
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2005
- 2005-06-29 AR ARP050102702A patent/AR049560A2/es unknown
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2006
- 2006-09-27 AU AU2006222711A patent/AU2006222711A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| SA01220270B1 (ar) | 2006-11-14 |
| IL151551A0 (en) | 2003-04-10 |
| AU5092001A (en) | 2001-10-15 |
| CA2403635A1 (en) | 2001-10-11 |
| SK14832002A3 (sk) | 2003-02-04 |
| BG107165A (bg) | 2003-07-31 |
| KR20030011807A (ko) | 2003-02-11 |
| AR033360A1 (es) | 2003-12-17 |
| NO20024679D0 (no) | 2002-09-30 |
| TWI284640B (en) | 2007-08-01 |
| AU2001250920B2 (en) | 2006-06-29 |
| PL359727A1 (en) | 2004-09-06 |
| EP1268442A2 (en) | 2003-01-02 |
| AR049560A2 (es) | 2006-08-16 |
| HUP0302675A2 (hu) | 2003-12-29 |
| JP2003529592A (ja) | 2003-10-07 |
| MY128296A (en) | 2007-01-31 |
| CN1330639C (zh) | 2007-08-08 |
| PE20011232A1 (es) | 2001-12-08 |
| SA06270303B1 (ar) | 2009-08-02 |
| NZ521183A (en) | 2004-03-26 |
| BR0109433A (pt) | 2004-08-10 |
| WO2001074787A2 (en) | 2001-10-11 |
| CN101066952A (zh) | 2007-11-07 |
| NO20024679L (no) | 2002-09-30 |
| KR100773258B1 (ko) | 2007-11-05 |
| WO2001074787A3 (en) | 2002-02-07 |
| MXPA02009559A (es) | 2003-05-21 |
| AU2006222711A1 (en) | 2006-10-19 |
| CZ20023529A3 (cs) | 2003-02-12 |
| CN1422259A (zh) | 2003-06-04 |
| HUP0302675A3 (en) | 2004-03-29 |
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