NO320367B1 - Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav - Google Patents
Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav Download PDFInfo
- Publication number
- NO320367B1 NO320367B1 NO19981205A NO981205A NO320367B1 NO 320367 B1 NO320367 B1 NO 320367B1 NO 19981205 A NO19981205 A NO 19981205A NO 981205 A NO981205 A NO 981205A NO 320367 B1 NO320367 B1 NO 320367B1
- Authority
- NO
- Norway
- Prior art keywords
- amino
- ethyl
- lower alkyl
- ch2n
- methyl
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 149
- 238000009472 formulation Methods 0.000 title claims abstract description 63
- YRHRIQCWCFGUEQ-UHFFFAOYSA-N thioxanthen-9-one Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3SC2=C1 YRHRIQCWCFGUEQ-UHFFFAOYSA-N 0.000 title abstract description 5
- 230000000259 anti-tumor effect Effects 0.000 title description 6
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 30
- 239000005720 sucrose Substances 0.000 claims abstract description 21
- 229930006000 Sucrose Natural products 0.000 claims abstract description 20
- 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 claims abstract description 20
- 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 claims abstract description 13
- 229930195725 Mannitol Natural products 0.000 claims abstract description 13
- 239000000594 mannitol Substances 0.000 claims abstract description 13
- 235000010355 mannitol Nutrition 0.000 claims abstract description 13
- 239000003381 stabilizer Substances 0.000 claims abstract description 12
- 239000002246 antineoplastic agent Substances 0.000 claims abstract description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims abstract description 8
- 239000000872 buffer Substances 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 88
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 68
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 64
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 59
- 125000000217 alkyl group Chemical group 0.000 claims description 36
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 29
- 239000001257 hydrogen Substances 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 20
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 18
- 150000002431 hydrogen Chemical class 0.000 claims description 12
- -1 methoxy, hydroxy Chemical group 0.000 claims description 10
- 239000011780 sodium chloride Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 241000124008 Mammalia Species 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 239000012453 solvate Substances 0.000 claims description 4
- 239000012931 lyophilized formulation Substances 0.000 claims description 2
- 229940001447 lactate Drugs 0.000 claims 4
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical group C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims 3
- 239000001540 sodium lactate Substances 0.000 claims 3
- 229940005581 sodium lactate Drugs 0.000 claims 3
- 235000011088 sodium lactate Nutrition 0.000 claims 3
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 208000013076 thyroid tumor Diseases 0.000 claims 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 184
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 96
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
- 239000000243 solution Substances 0.000 description 69
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 68
- 239000000047 product Substances 0.000 description 64
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 49
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 42
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 42
- 238000000034 method Methods 0.000 description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 35
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 32
- 239000011541 reaction mixture Substances 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 28
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 28
- 235000019439 ethyl acetate Nutrition 0.000 description 28
- 239000007787 solid Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- 239000012044 organic layer Substances 0.000 description 24
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 23
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 23
- 239000002904 solvent Substances 0.000 description 23
- 238000001035 drying Methods 0.000 description 22
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 22
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- ATHHXGZTWNVVOU-UHFFFAOYSA-N N-methylformamide Chemical compound CNC=O ATHHXGZTWNVVOU-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- 238000004108 freeze drying Methods 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 239000012458 free base Substances 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 17
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
- 238000003860 storage Methods 0.000 description 16
- 230000009477 glass transition Effects 0.000 description 14
- 239000000377 silicon dioxide Substances 0.000 description 14
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- 238000003818 flash chromatography Methods 0.000 description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 235000019253 formic acid Nutrition 0.000 description 11
- 229940098779 methanesulfonic acid Drugs 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 238000007792 addition Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 150000001412 amines Chemical class 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- YKGMKSIHIVVYKY-UHFFFAOYSA-N dabrafenib mesylate Chemical compound CS(O)(=O)=O.S1C(C(C)(C)C)=NC(C=2C(=C(NS(=O)(=O)C=3C(=CC=CC=3F)F)C=CC=2)F)=C1C1=CC=NC(N)=N1 YKGMKSIHIVVYKY-UHFFFAOYSA-N 0.000 description 8
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
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- 239000005457 ice water Substances 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 7
- 239000000843 powder Substances 0.000 description 7
- XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical group N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 6
- RPGMVOVTCDJHJS-UHFFFAOYSA-N 4-(aminomethyl)-1-[2-(diethylamino)ethylamino]thioxanthen-9-one Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CN)=CC=C2NCCN(CC)CC RPGMVOVTCDJHJS-UHFFFAOYSA-N 0.000 description 6
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- OPQARKPSCNTWTJ-UHFFFAOYSA-L copper(ii) acetate Chemical compound [Cu+2].CC([O-])=O.CC([O-])=O OPQARKPSCNTWTJ-UHFFFAOYSA-L 0.000 description 6
- 238000002425 crystallisation Methods 0.000 description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
- NAMOLZVVTPNNTE-UHFFFAOYSA-N n-[[1-[2-(diethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]methanesulfonamide Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CNS(C)(=O)=O)=CC=C2NCCN(CC)CC NAMOLZVVTPNNTE-UHFFFAOYSA-N 0.000 description 6
- 239000000546 pharmaceutical excipient Substances 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
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- YISDJDCPIOLYQH-UHFFFAOYSA-N 7-bromo-1-[2-(diethylamino)ethylamino]-9-oxothioxanthene-4-carbaldehyde Chemical compound S1C2=CC=C(Br)C=C2C(=O)C2=C1C(C=O)=CC=C2NCCN(CC)CC YISDJDCPIOLYQH-UHFFFAOYSA-N 0.000 description 2
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- BTAIDSUUTQCVEU-UHFFFAOYSA-N n-[[1-[2-(diethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]-n-methylbenzenesulfonamide;methanesulfonic acid Chemical compound CS(O)(=O)=O.C1=2SC3=CC=CC=C3C(=O)C=2C(NCCN(CC)CC)=CC=C1CN(C)S(=O)(=O)C1=CC=CC=C1 BTAIDSUUTQCVEU-UHFFFAOYSA-N 0.000 description 1
- GDFHUNCQGDODEI-UHFFFAOYSA-N n-[[1-[2-(dimethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]formamide Chemical compound S1C2=CC=CC=C2C(=O)C2=C1C(CNC=O)=CC=C2NCCN(C)C GDFHUNCQGDODEI-UHFFFAOYSA-N 0.000 description 1
- ASVIZOWWEUBBPD-UHFFFAOYSA-N n-[[7-bromo-1-[2-(diethylamino)ethylamino]-9-oxothioxanthen-4-yl]methyl]formamide Chemical compound S1C2=CC=C(Br)C=C2C(=O)C2=C1C(CNC=O)=CC=C2NCCN(CC)CC ASVIZOWWEUBBPD-UHFFFAOYSA-N 0.000 description 1
- PVWOIHVRPOBWPI-UHFFFAOYSA-N n-propyl iodide Chemical compound CCCI PVWOIHVRPOBWPI-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 201000008129 pancreatic ductal adenocarcinoma Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 238000010587 phase diagram Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 229940071643 prefilled syringe Drugs 0.000 description 1
- 238000011165 process development Methods 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- ROSDSFDQCJNGOL-UHFFFAOYSA-N protonated dimethyl amine Natural products CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000010512 thermal transition Effects 0.000 description 1
- NBOMNTLFRHMDEZ-UHFFFAOYSA-N thiosalicylic acid Chemical compound OC(=O)C1=CC=CC=C1S NBOMNTLFRHMDEZ-UHFFFAOYSA-N 0.000 description 1
- 229940103494 thiosalicylic acid Drugs 0.000 description 1
- KZZBVWCQFFXEPH-UHFFFAOYSA-N thioxanthen-9-one dihydrochloride Chemical compound Cl.Cl.C1=CC=CC=2SC3=CC=CC=C3C(C12)=O KZZBVWCQFFXEPH-UHFFFAOYSA-N 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- PNQBEPDZQUOCNY-UHFFFAOYSA-N trifluoroacetyl chloride Chemical compound FC(F)(F)C(Cl)=O PNQBEPDZQUOCNY-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000004017 vitrification Methods 0.000 description 1
- 239000008215 water for injection Substances 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/67—Phosphorus compounds having sulfur as a ring hetero atom
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/382—Heterocyclic compounds having sulfur as a ring hetero atom having six-membered rings, e.g. thioxanthenes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Food Preservation Except Freezing, Refrigeration, And Drying (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/529,934 US5665760A (en) | 1995-09-18 | 1995-09-18 | Lyophilized thioxanthenone antitumor agents |
| PCT/IB1996/000984 WO1997010809A1 (en) | 1995-09-18 | 1996-09-12 | Lyophilized thioxanthenone antimumor agents |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO981205D0 NO981205D0 (no) | 1998-03-17 |
| NO981205L NO981205L (no) | 1998-05-15 |
| NO320367B1 true NO320367B1 (no) | 2005-11-28 |
Family
ID=24111801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19981205A NO320367B1 (no) | 1995-09-18 | 1998-03-17 | Lyofiliserte tioxantenon-antitumorformuleringer og anvendelse derav |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5665760A (es) |
| EP (1) | EP0917458B1 (es) |
| JP (1) | JP2001503374A (es) |
| KR (1) | KR100475385B1 (es) |
| CN (1) | CN1178651C (es) |
| AT (1) | ATE235888T1 (es) |
| AU (1) | AU716782B2 (es) |
| CA (1) | CA2232444A1 (es) |
| CZ (1) | CZ293433B6 (es) |
| DE (1) | DE69627209T2 (es) |
| DK (1) | DK0917458T3 (es) |
| ES (1) | ES2196171T3 (es) |
| HK (1) | HK1016891A1 (es) |
| HU (1) | HUP9900246A3 (es) |
| NO (1) | NO320367B1 (es) |
| NZ (1) | NZ316609A (es) |
| PL (1) | PL185164B1 (es) |
| PT (1) | PT917458E (es) |
| RU (1) | RU2157189C2 (es) |
| WO (1) | WO1997010809A1 (es) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5952300A (en) * | 1996-04-19 | 1999-09-14 | Merck & Co., Inc. | Antifungal compositions |
| US6407278B2 (en) * | 1998-11-16 | 2002-06-18 | Medimmune Oncology, Inc. | Stable amorphous amifostine compositions and methods for the preparation and use of the same |
| GB0115893D0 (en) * | 2001-06-28 | 2001-08-22 | Sanofi Synthelabo | Formulations |
| US7378408B2 (en) * | 2001-11-30 | 2008-05-27 | Pfizer Inc. | Methods of treatment and formulations of cephalosporin |
| JP2007526329A (ja) * | 2004-03-04 | 2007-09-13 | ワイス | 賦形剤の結晶化を改善するための凍結乾燥法 |
| WO2007075452A2 (en) * | 2005-12-16 | 2007-07-05 | Wyeth | Lyophilized compositions of a triazolopyrimidine compound |
| TW201021855A (en) * | 2008-11-13 | 2010-06-16 | Taigen Biotechnology Co Ltd | Lyophilization formulation |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4582851A (en) * | 1984-02-06 | 1986-04-15 | Warner-Lambert Company | Anti-bacterial 1,4-aminoalkylamino-9H-thioxanthen-9-one derivatives, compositions, and method of use therefor |
| US5091410A (en) * | 1991-06-10 | 1992-02-25 | Sterling Winthrop Inc. | Thioxanthenone antitumor agents |
| AU642596B2 (en) * | 1991-06-10 | 1993-10-21 | Sanofi-Synthelabo | Thioxanthenone antitumor agents |
| US5346917A (en) * | 1991-06-10 | 1994-09-13 | Sterling Winthrop Inc. | Thioxanthenone antitumor agents |
-
1995
- 1995-09-18 US US08/529,934 patent/US5665760A/en not_active Expired - Fee Related
-
1996
- 1996-09-12 DK DK96929491T patent/DK0917458T3/da active
- 1996-09-12 PL PL96325603A patent/PL185164B1/pl not_active IP Right Cessation
- 1996-09-12 CA CA002232444A patent/CA2232444A1/en not_active Abandoned
- 1996-09-12 CZ CZ1998799A patent/CZ293433B6/cs not_active IP Right Cessation
- 1996-09-12 RU RU98107334/14A patent/RU2157189C2/ru not_active IP Right Cessation
- 1996-09-12 JP JP51253097A patent/JP2001503374A/ja not_active Ceased
- 1996-09-12 HU HU9900246A patent/HUP9900246A3/hu unknown
- 1996-09-12 DE DE69627209T patent/DE69627209T2/de not_active Expired - Fee Related
- 1996-09-12 PT PT96929491T patent/PT917458E/pt unknown
- 1996-09-12 KR KR1019980701983A patent/KR100475385B1/ko not_active IP Right Cessation
- 1996-09-12 NZ NZ316609A patent/NZ316609A/xx unknown
- 1996-09-12 WO PCT/IB1996/000984 patent/WO1997010809A1/en active IP Right Grant
- 1996-09-12 AT AT96929491T patent/ATE235888T1/de not_active IP Right Cessation
- 1996-09-12 EP EP96929491A patent/EP0917458B1/en not_active Expired - Lifetime
- 1996-09-12 ES ES96929491T patent/ES2196171T3/es not_active Expired - Lifetime
- 1996-09-12 CN CNB961981741A patent/CN1178651C/zh not_active Expired - Fee Related
- 1996-09-12 AU AU68880/96A patent/AU716782B2/en not_active Ceased
-
1998
- 1998-03-17 NO NO19981205A patent/NO320367B1/no unknown
-
1999
- 1999-05-06 HK HK99102048A patent/HK1016891A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| RU2157189C2 (ru) | 2000-10-10 |
| DE69627209D1 (en) | 2003-05-08 |
| AU716782B2 (en) | 2000-03-09 |
| PT917458E (pt) | 2003-08-29 |
| EP0917458B1 (en) | 2003-04-02 |
| NO981205L (no) | 1998-05-15 |
| HUP9900246A3 (en) | 2002-12-28 |
| US5665760A (en) | 1997-09-09 |
| ATE235888T1 (de) | 2003-04-15 |
| CN1201387A (zh) | 1998-12-09 |
| HUP9900246A2 (hu) | 2001-04-28 |
| NZ316609A (en) | 1999-05-28 |
| MX9802143A (es) | 1998-05-31 |
| CA2232444A1 (en) | 1997-03-27 |
| DK0917458T3 (da) | 2003-07-28 |
| PL325603A1 (en) | 1998-08-03 |
| CN1178651C (zh) | 2004-12-08 |
| NO981205D0 (no) | 1998-03-17 |
| PL185164B1 (pl) | 2003-03-31 |
| HK1016891A1 (en) | 1999-11-12 |
| WO1997010809A1 (en) | 1997-03-27 |
| CZ79998A3 (cs) | 1998-08-12 |
| ES2196171T3 (es) | 2003-12-16 |
| EP0917458A1 (en) | 1999-05-26 |
| KR19990045741A (ko) | 1999-06-25 |
| AU6888096A (en) | 1997-04-09 |
| KR100475385B1 (ko) | 2006-03-23 |
| CZ293433B6 (cs) | 2004-04-14 |
| JP2001503374A (ja) | 2001-03-13 |
| DE69627209T2 (de) | 2004-02-19 |
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