CN1030610C - 制备结晶的鬼臼乙叉甙4’-磷酸酯二乙醇化物的新方法 - Google Patents
制备结晶的鬼臼乙叉甙4’-磷酸酯二乙醇化物的新方法 Download PDFInfo
- Publication number
- CN1030610C CN1030610C CN92111350A CN92111350A CN1030610C CN 1030610 C CN1030610 C CN 1030610C CN 92111350 A CN92111350 A CN 92111350A CN 92111350 A CN92111350 A CN 92111350A CN 1030610 C CN1030610 C CN 1030610C
- Authority
- CN
- China
- Prior art keywords
- zuyeyidal
- solution
- acid ester
- phosphoric acid
- alcoholate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title claims abstract description 21
- 238000002360 preparation method Methods 0.000 title description 9
- LIQODXNTTZAGID-OCBXBXKTSA-N etoposide phosphate Chemical compound COC1=C(OP(O)(O)=O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 LIQODXNTTZAGID-OCBXBXKTSA-N 0.000 title description 2
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 73
- 229960005420 etoposide Drugs 0.000 claims description 73
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 36
- 239000000243 solution Substances 0.000 claims description 35
- 238000002425 crystallisation Methods 0.000 claims description 27
- 230000008025 crystallization Effects 0.000 claims description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 22
- 150000003014 phosphoric acid esters Chemical class 0.000 claims description 17
- 239000000047 product Substances 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 229960004756 ethanol Drugs 0.000 claims description 10
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 6
- 239000000706 filtrate Substances 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 3
- 238000010992 reflux Methods 0.000 claims description 3
- 239000012047 saturated solution Substances 0.000 claims description 3
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 1
- 238000013019 agitation Methods 0.000 claims 1
- 230000001476 alcoholic effect Effects 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 5
- 238000001291 vacuum drying Methods 0.000 description 5
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 235000010169 Podophyllum emodi Nutrition 0.000 description 4
- 241000332712 Sinopodophyllum hexandrum Species 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 229930182478 glucoside Natural products 0.000 description 4
- 150000008131 glucosides Chemical class 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 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 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000004809 Teflon Substances 0.000 description 2
- 229920006362 Teflon® Polymers 0.000 description 2
- YADJFRGSGWGMNH-UHFFFAOYSA-N [chloro(phenylmethoxy)phosphoryl]oxymethylbenzene Chemical compound C=1C=CC=CC=1COP(=O)(Cl)OCC1=CC=CC=C1 YADJFRGSGWGMNH-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 239000003791 organic solvent mixture Substances 0.000 description 2
- -1 phosphate diethanol compound Chemical class 0.000 description 2
- 230000035479 physiological effects, processes and functions Effects 0.000 description 2
- 238000000634 powder X-ray diffraction Methods 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- 239000008247 solid mixture Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 229940038773 trisodium citrate Drugs 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 1
- 239000004254 Ammonium phosphate Substances 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 239000001828 Gelatine Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001274216 Naso Species 0.000 description 1
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000004411 aluminium Substances 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
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910000148 ammonium phosphate Inorganic materials 0.000 description 1
- 235000019289 ammonium phosphates Nutrition 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- NMGSDTSOSIPXTN-UHFFFAOYSA-N cyclohexa-1,2-diene Chemical compound C1CC=C=CC1 NMGSDTSOSIPXTN-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- MNNHAPBLZZVQHP-UHFFFAOYSA-N diammonium hydrogen phosphate Chemical compound [NH4+].[NH4+].OP([O-])([O-])=O MNNHAPBLZZVQHP-UHFFFAOYSA-N 0.000 description 1
- HDFFVHSMHLDSLO-UHFFFAOYSA-M dibenzyl phosphate Chemical compound C=1C=CC=CC=1COP(=O)([O-])OCC1=CC=CC=C1 HDFFVHSMHLDSLO-UHFFFAOYSA-M 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- HXBZCHYDLURWIZ-UHFFFAOYSA-N diphenyl hydrogen phosphate;hydrochloride Chemical compound Cl.C=1C=CC=CC=1OP(=O)(O)OC1=CC=CC=C1 HXBZCHYDLURWIZ-UHFFFAOYSA-N 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 239000005308 flint glass Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002715 modification method Methods 0.000 description 1
- 208000025189 neoplasm of testis Diseases 0.000 description 1
- 238000011275 oncology therapy Methods 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N phosphoric acid Substances OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000007738 vacuum evaporation Methods 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/773,056 US5648474A (en) | 1991-10-08 | 1991-10-08 | Crystalline etoposide 4'-phosphate diethanolate |
| US773,056 | 1991-10-08 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1071432A CN1071432A (zh) | 1993-04-28 |
| CN1030610C true CN1030610C (zh) | 1996-01-03 |
Family
ID=25097069
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN92111350A Expired - Lifetime CN1030610C (zh) | 1991-10-08 | 1992-09-30 | 制备结晶的鬼臼乙叉甙4’-磷酸酯二乙醇化物的新方法 |
Country Status (27)
| Country | Link |
|---|---|
| US (1) | US5648474A (OSRAM) |
| EP (1) | EP0537555B1 (OSRAM) |
| JP (1) | JP3205816B2 (OSRAM) |
| KR (1) | KR100243981B1 (OSRAM) |
| CN (1) | CN1030610C (OSRAM) |
| AT (1) | ATE156832T1 (OSRAM) |
| AU (1) | AU650572B2 (OSRAM) |
| CA (1) | CA2079581C (OSRAM) |
| CZ (1) | CZ283735B6 (OSRAM) |
| DE (1) | DE69221573T2 (OSRAM) |
| DK (1) | DK0537555T3 (OSRAM) |
| EG (1) | EG20187A (OSRAM) |
| ES (1) | ES2109970T3 (OSRAM) |
| FI (1) | FI105034B (OSRAM) |
| GR (1) | GR3025176T3 (OSRAM) |
| HU (2) | HU213606B (OSRAM) |
| IL (1) | IL103262A (OSRAM) |
| MX (1) | MX9205777A (OSRAM) |
| MY (1) | MY108969A (OSRAM) |
| NO (1) | NO178342C (OSRAM) |
| NZ (1) | NZ244521A (OSRAM) |
| PH (1) | PH31666A (OSRAM) |
| PL (1) | PL168332B1 (OSRAM) |
| RU (1) | RU2042686C1 (OSRAM) |
| SK (1) | SK278935B6 (OSRAM) |
| TW (1) | TW239863B (OSRAM) |
| ZA (1) | ZA926903B (OSRAM) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5459248A (en) * | 1993-11-04 | 1995-10-17 | Bristol-Myers Squibb Company | Process of preparing etoposide phosphate and etoposide |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4914222A (en) * | 1983-08-29 | 1990-04-03 | Merck & Co., Inc. | Crystalline salts of L or (S)-3-(3,4-dihydroxyphenyl)-2-methylalanine esters and process |
| US4670578A (en) * | 1983-08-29 | 1987-06-02 | Merck & Co., Inc. | Process for crystalline salts of L or (S)-3-(3,4-dihydroxyphenyl)-2-methylalanine esters |
| US4713246A (en) * | 1984-03-19 | 1987-12-15 | Bristol-Myers Company | Etoposide oral dosage form |
| US4775751A (en) * | 1985-06-03 | 1988-10-04 | Eli Lilly & Company | Process for cephalexin hydrochloride alcoholates |
| US4927638A (en) * | 1986-10-08 | 1990-05-22 | Bristol-Myers Company | Etoposide solutions |
| US4904768A (en) * | 1987-08-04 | 1990-02-27 | Bristol-Myers Company | Epipodophyllotoxin glucoside 4'-phosphate derivatives |
| ES2061891T3 (es) * | 1988-11-16 | 1994-12-16 | Nippon Kayaku Kk | Cristales de dihidrato de dihidrocloruro de compuesto de etoposido-2-dimetilamina y un procedimiento para su produccion. |
| US5081234A (en) * | 1990-04-30 | 1992-01-14 | Bristol-Myers Squibb Co. | 4'-demethylepipodophyllotoxin glycosides |
-
1991
- 1991-10-08 US US07/773,056 patent/US5648474A/en not_active Expired - Lifetime
-
1992
- 1992-03-07 TW TW081101734A patent/TW239863B/zh not_active IP Right Cessation
- 1992-09-10 ZA ZA926903A patent/ZA926903B/xx unknown
- 1992-09-11 MY MYPI92001632A patent/MY108969A/en unknown
- 1992-09-22 JP JP30024092A patent/JP3205816B2/ja not_active Expired - Lifetime
- 1992-09-23 IL IL103262A patent/IL103262A/xx not_active IP Right Cessation
- 1992-09-23 AU AU25301/92A patent/AU650572B2/en not_active Expired
- 1992-09-26 EG EG56692A patent/EG20187A/xx active
- 1992-09-28 NZ NZ244521A patent/NZ244521A/en not_active IP Right Cessation
- 1992-09-28 NO NO923754A patent/NO178342C/no not_active IP Right Cessation
- 1992-09-29 PL PL92296078A patent/PL168332B1/pl unknown
- 1992-09-29 FI FI924359A patent/FI105034B/fi not_active IP Right Cessation
- 1992-09-30 CA CA002079581A patent/CA2079581C/en not_active Expired - Lifetime
- 1992-09-30 HU HU9203119A patent/HU213606B/hu unknown
- 1992-09-30 AT AT92116749T patent/ATE156832T1/de active
- 1992-09-30 CZ CS922986A patent/CZ283735B6/cs not_active IP Right Cessation
- 1992-09-30 EP EP92116749A patent/EP0537555B1/en not_active Expired - Lifetime
- 1992-09-30 DK DK92116749.0T patent/DK0537555T3/da active
- 1992-09-30 DE DE69221573T patent/DE69221573T2/de not_active Expired - Lifetime
- 1992-09-30 SK SK2986-92A patent/SK278935B6/sk not_active IP Right Cessation
- 1992-09-30 ES ES92116749T patent/ES2109970T3/es not_active Expired - Lifetime
- 1992-09-30 PH PH45023A patent/PH31666A/en unknown
- 1992-09-30 RU SU925052958A patent/RU2042686C1/ru active
- 1992-09-30 CN CN92111350A patent/CN1030610C/zh not_active Expired - Lifetime
- 1992-10-01 KR KR1019920018032A patent/KR100243981B1/ko not_active Expired - Lifetime
- 1992-10-08 MX MX9205777A patent/MX9205777A/es unknown
-
1995
- 1995-06-22 HU HU95P/P00385P patent/HU211672A9/hu unknown
-
1997
- 1997-10-29 GR GR970402811T patent/GR3025176T3/el unknown
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