CA2140013C - Pharmaceutical compositions containing galactosylceramides - Google Patents
Pharmaceutical compositions containing galactosylceramides Download PDFInfo
- Publication number
- CA2140013C CA2140013C CA002140013A CA2140013A CA2140013C CA 2140013 C CA2140013 C CA 2140013C CA 002140013 A CA002140013 A CA 002140013A CA 2140013 A CA2140013 A CA 2140013A CA 2140013 C CA2140013 C CA 2140013C
- Authority
- CA
- Canada
- Prior art keywords
- integer
- alpha
- galactopyranosyloxy
- set forth
- formula
- 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 - Fee Related
Links
- 239000008194 pharmaceutical composition Substances 0.000 title abstract description 3
- 150000002254 galactosylceramides Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 268
- 239000003814 drug Substances 0.000 claims abstract description 80
- 206010043554 thrombocytopenia Diseases 0.000 claims abstract description 67
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 59
- 230000004663 cell proliferation Effects 0.000 claims abstract description 58
- 239000000718 radiation-protective agent Substances 0.000 claims abstract description 58
- 125000001424 substituent group Chemical group 0.000 claims abstract description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 10
- 125000002347 octyl 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])[H] 0.000 claims abstract 4
- 230000000694 effects Effects 0.000 claims description 52
- 210000004027 cell Anatomy 0.000 claims description 32
- 210000001772 blood platelet Anatomy 0.000 claims description 26
- 230000005855 radiation Effects 0.000 claims description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 201000010099 disease Diseases 0.000 claims description 16
- 241000282414 Homo sapiens Species 0.000 claims description 14
- 238000011282 treatment Methods 0.000 claims description 13
- 238000001959 radiotherapy Methods 0.000 claims description 12
- 230000007423 decrease Effects 0.000 claims description 9
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 239000002246 antineoplastic agent Substances 0.000 claims description 6
- 230000003247 decreasing effect Effects 0.000 claims description 5
- 238000002512 chemotherapy Methods 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 238000011321 prophylaxis Methods 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 208000019838 Blood disease Diseases 0.000 claims description 2
- 208000035473 Communicable disease Diseases 0.000 claims description 2
- 206010041660 Splenomegaly Diseases 0.000 claims description 2
- 231100001015 blood dyscrasias Toxicity 0.000 claims description 2
- 208000019425 cirrhosis of liver Diseases 0.000 claims description 2
- 208000014951 hematologic disease Diseases 0.000 claims description 2
- 208000018706 hematopoietic system disease Diseases 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 230000009897 systematic effect Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 3
- 230000001133 acceleration Effects 0.000 claims 1
- 230000005779 cell damage Effects 0.000 claims 1
- 208000037887 cell injury Diseases 0.000 claims 1
- 231100000518 lethal Toxicity 0.000 claims 1
- 230000001665 lethal effect Effects 0.000 claims 1
- WDUMAPVMFPPSOU-UHFFFAOYSA-N octadecan-3-ol Chemical compound CCCCCCCCCCCCCCCC(O)CC WDUMAPVMFPPSOU-UHFFFAOYSA-N 0.000 claims 1
- 238000003786 synthesis reaction Methods 0.000 description 142
- 230000015572 biosynthetic process Effects 0.000 description 140
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 92
- 239000000203 mixture Substances 0.000 description 76
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 69
- 238000000434 field desorption mass spectrometry Methods 0.000 description 68
- 238000000034 method Methods 0.000 description 64
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 59
- 238000006243 chemical reaction Methods 0.000 description 53
- 239000000243 solution Substances 0.000 description 48
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 46
- 239000000499 gel Substances 0.000 description 41
- 239000000741 silica gel Substances 0.000 description 41
- 229910002027 silica gel Inorganic materials 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 36
- 238000000746 purification Methods 0.000 description 33
- 101150041968 CDC13 gene Proteins 0.000 description 32
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 32
- 150000001412 amines Chemical class 0.000 description 29
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 27
- 229940126208 compound 22 Drugs 0.000 description 27
- 150000001299 aldehydes Chemical class 0.000 description 23
- 239000000706 filtrate Substances 0.000 description 23
- 101710200114 Cysteine proteinase inhibitor 10 Proteins 0.000 description 22
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 20
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- USHLGTXWTJINJU-RUZDIDTESA-N (2r)-2-acetyloxytetracosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCC[C@H](C(O)=O)OC(C)=O USHLGTXWTJINJU-RUZDIDTESA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 150000003839 salts Chemical class 0.000 description 17
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- 229940125904 compound 1 Drugs 0.000 description 15
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000001257 hydrogen Substances 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 230000002194 synthesizing effect Effects 0.000 description 14
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 13
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 229940125898 compound 5 Drugs 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- 229940126639 Compound 33 Drugs 0.000 description 11
- 238000010586 diagram Methods 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 10
- 241000282693 Cercopithecidae Species 0.000 description 10
- PNUZDKCDAWUEGK-CYZMBNFOSA-N Sitafloxacin Chemical compound C([C@H]1N)N(C=2C(=C3C(C(C(C(O)=O)=CN3[C@H]3[C@H](C3)F)=O)=CC=2F)Cl)CC11CC1 PNUZDKCDAWUEGK-CYZMBNFOSA-N 0.000 description 10
- 150000001408 amides Chemical class 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- 150000002431 hydrogen Chemical class 0.000 description 10
- 230000009467 reduction Effects 0.000 description 10
- 238000006722 reduction reaction Methods 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 239000003981 vehicle Substances 0.000 description 10
- WMUWPEDLXNSDFU-UHFFFAOYSA-N (4-nitrophenyl) tetracosanoate Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(=O)OC1=CC=C([N+]([O-])=O)C=C1 WMUWPEDLXNSDFU-UHFFFAOYSA-N 0.000 description 9
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- GGIDEJQGAZSTES-UHFFFAOYSA-N (4-nitrophenyl) octanoate Chemical compound CCCCCCCC(=O)OC1=CC=C([N+]([O-])=O)C=C1 GGIDEJQGAZSTES-UHFFFAOYSA-N 0.000 description 8
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- -1 aldehyde compound Chemical class 0.000 description 8
- 238000010511 deprotection reaction Methods 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 7
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 7
- CQXMAMUUWHYSIY-UHFFFAOYSA-N Lignoceric acid Natural products CCCCCCCCCCCCCCCCCCCCCCCC(=O)OCCC1=CC=C(O)C=C1 CQXMAMUUWHYSIY-UHFFFAOYSA-N 0.000 description 7
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 7
- 150000001540 azides Chemical class 0.000 description 7
- 229940106189 ceramide Drugs 0.000 description 7
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- QZZGJDVWLFXDLK-UHFFFAOYSA-N tetracosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(O)=O QZZGJDVWLFXDLK-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 6
- RBWNDBNSJFCLBZ-UHFFFAOYSA-N 7-methyl-5,6,7,8-tetrahydro-3h-[1]benzothiolo[2,3-d]pyrimidine-4-thione Chemical compound N1=CNC(=S)C2=C1SC1=C2CCC(C)C1 RBWNDBNSJFCLBZ-UHFFFAOYSA-N 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 6
- 229940125773 compound 10 Drugs 0.000 description 6
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 6
- 231100000636 lethal dose Toxicity 0.000 description 6
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- 239000000463 material Substances 0.000 description 6
- 239000002808 molecular sieve Substances 0.000 description 6
- 230000000144 pharmacologic effect Effects 0.000 description 6
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 6
- 239000001119 stannous chloride Substances 0.000 description 6
- 235000011150 stannous chloride Nutrition 0.000 description 6
- RIUZWTBPMXBVKC-YMWOCUMHSA-N (3r,4s,5r,6r)-2-benzyl-2-fluoro-6-(hydroxymethyl)oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)OC1(F)CC1=CC=CC=C1 RIUZWTBPMXBVKC-YMWOCUMHSA-N 0.000 description 5
- 235000021353 Lignoceric acid Nutrition 0.000 description 5
- 230000009435 amidation Effects 0.000 description 5
- 238000007112 amidation reaction Methods 0.000 description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 210000004700 fetal blood Anatomy 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 210000003462 vein Anatomy 0.000 description 5
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 4
- KOFLVDBWRHFSAB-UHFFFAOYSA-N 1,2,4,5-tetrahydro-1-(phenylmethyl)-5,9b(1',2')-benzeno-9bh-benz(g)indol-3(3ah)-one Chemical compound C1C(C=2C3=CC=CC=2)C2=CC=CC=C2C23C1C(=O)CN2CC1=CC=CC=C1 KOFLVDBWRHFSAB-UHFFFAOYSA-N 0.000 description 4
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 4
- HTFNVAVTYILUCF-UHFFFAOYSA-N 2-[2-ethoxy-4-[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]anilino]-5-methyl-11-methylsulfonylpyrimido[4,5-b][1,4]benzodiazepin-6-one Chemical compound CCOc1cc(ccc1Nc1ncc2N(C)C(=O)c3ccccc3N(c2n1)S(C)(=O)=O)C(=O)N1CCC(CC1)N1CCN(C)CC1 HTFNVAVTYILUCF-UHFFFAOYSA-N 0.000 description 4
- UOXJNGFFPMOZDM-UHFFFAOYSA-N 2-[di(propan-2-yl)amino]ethylsulfanyl-methylphosphinic acid Chemical compound CC(C)N(C(C)C)CCSP(C)(O)=O UOXJNGFFPMOZDM-UHFFFAOYSA-N 0.000 description 4
- FJXJAAFKONAPKR-UHFFFAOYSA-N 4-methoxy-2-nitrobenzo[e][1]benzofuran Chemical compound COC1=CC2=CC=CC=C2C2=C1OC([N+]([O-])=O)=C2 FJXJAAFKONAPKR-UHFFFAOYSA-N 0.000 description 4
- NYIVWTWKIQOBKO-UHFFFAOYSA-N 4-phenanthren-3-ylbutanoic acid Chemical compound C1=CC=C2C3=CC(CCCC(=O)O)=CC=C3C=CC2=C1 NYIVWTWKIQOBKO-UHFFFAOYSA-N 0.000 description 4
- QDDQSSZZYNCVHC-UHFFFAOYSA-N 5-[(4-tert-butylphenoxy)carbonylamino]-2-hydroxybenzoic acid Chemical compound C1=CC(C(C)(C)C)=CC=C1OC(=O)NC1=CC=C(O)C(C(O)=O)=C1 QDDQSSZZYNCVHC-UHFFFAOYSA-N 0.000 description 4
- SFHYNDMGZXWXBU-LIMNOBDPSA-N 6-amino-2-[[(e)-(3-formylphenyl)methylideneamino]carbamoylamino]-1,3-dioxobenzo[de]isoquinoline-5,8-disulfonic acid Chemical compound O=C1C(C2=3)=CC(S(O)(=O)=O)=CC=3C(N)=C(S(O)(=O)=O)C=C2C(=O)N1NC(=O)N\N=C\C1=CC=CC(C=O)=C1 SFHYNDMGZXWXBU-LIMNOBDPSA-N 0.000 description 4
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- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
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- NSGDYZCDUPSTQT-UHFFFAOYSA-N N-[5-bromo-1-[(4-fluorophenyl)methyl]-4-methyl-2-oxopyridin-3-yl]cycloheptanecarboxamide Chemical compound Cc1c(Br)cn(Cc2ccc(F)cc2)c(=O)c1NC(=O)C1CCCCCC1 NSGDYZCDUPSTQT-UHFFFAOYSA-N 0.000 description 4
- 239000012980 RPMI-1640 medium Substances 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- LJOOWESTVASNOG-UFJKPHDISA-N [(1s,3r,4ar,7s,8s,8as)-3-hydroxy-8-[2-[(4r)-4-hydroxy-6-oxooxan-2-yl]ethyl]-7-methyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-yl] (2s)-2-methylbutanoate Chemical compound C([C@H]1[C@@H](C)C=C[C@H]2C[C@@H](O)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)CC1C[C@@H](O)CC(=O)O1 LJOOWESTVASNOG-UFJKPHDISA-N 0.000 description 4
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 4
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- NKGQKEDEWMDQTO-UHFFFAOYSA-N tetradecane;triphenylphosphanium;bromide Chemical compound [Br-].CCCCCCCCCCCCCC.C1=CC=CC=C1[PH+](C=1C=CC=CC=1)C1=CC=CC=C1 NKGQKEDEWMDQTO-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001694 thigh bone Anatomy 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- OHSJPLSEQNCRLW-UHFFFAOYSA-N triphenylmethyl radical Chemical compound C1=CC=CC=C1[C](C=1C=CC=CC=1)C1=CC=CC=C1 OHSJPLSEQNCRLW-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
- C07H15/10—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical containing unsaturated carbon-to-carbon bonds
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/02—Acyclic radicals, not substituted by cyclic structures
- C07H15/04—Acyclic radicals, not substituted by cyclic structures attached to an oxygen atom of the saccharide radical
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Genetics & Genomics (AREA)
- Crystallography & Structural Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP212015/1992 | 1992-07-16 | ||
| JP21201592 | 1992-07-16 | ||
| JP85219/1993 | 1993-03-19 | ||
| JP8521993 | 1993-03-19 | ||
| PCT/JP1993/000984 WO1994002168A1 (fr) | 1992-07-16 | 1993-07-15 | Nouvelle composition medicamenteuse |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2140013A1 CA2140013A1 (en) | 1994-02-03 |
| CA2140013C true CA2140013C (en) | 2002-08-27 |
Family
ID=26426239
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002140013A Expired - Fee Related CA2140013C (en) | 1992-07-16 | 1993-07-15 | Pharmaceutical compositions containing galactosylceramides |
Country Status (12)
| Country | Link |
|---|---|
| US (3) | US5767092A (enExample) |
| EP (1) | EP0650732B1 (enExample) |
| JP (1) | JP3088461B2 (enExample) |
| KR (1) | KR100277621B1 (enExample) |
| CN (1) | CN1084623C (enExample) |
| AT (1) | ATE200224T1 (enExample) |
| AU (1) | AU684466B2 (enExample) |
| CA (1) | CA2140013C (enExample) |
| DE (1) | DE69330096T2 (enExample) |
| FI (1) | FI950166A7 (enExample) |
| TW (1) | TW261533B (enExample) |
| WO (1) | WO1994002168A1 (enExample) |
Families Citing this family (45)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5936076A (en) * | 1991-08-29 | 1999-08-10 | Kirin Beer Kabushiki Kaisha | αgalactosylceramide derivatives |
| AU683026B2 (en) * | 1992-10-22 | 1997-10-30 | Kirin Pharma Kabushiki Kaisha | Novel shingoglycolipid and use thereof |
| US5780441A (en) * | 1993-04-15 | 1998-07-14 | Kirin Beer Kabushiki Kaisha | Sphingoglycolipid compounds and therapeutic uses thereof |
| US6026815A (en) * | 1996-10-10 | 2000-02-22 | Gholam A. Peyman | Radiopaque liquid as radiation blocking agent |
| JP2002226377A (ja) * | 1996-10-14 | 2002-08-14 | Kirin Brewery Co Ltd | 配糖体含有末梢血幹細胞増加剤 |
| TW555562B (en) * | 1996-12-27 | 2003-10-01 | Kirin Brewery | Method for activation of human antigen-presenting cells, activated human antigen-presenting cells and use thereof |
| US6417167B1 (en) | 1997-02-05 | 2002-07-09 | Kirin Beer Kabushiki Kaisha | Lyophilized compositions containing shingoglycolipid and process for preparing them |
| CA2280130C (en) * | 1997-02-05 | 2007-12-18 | Kirin Beer Kabushiki Kaisha | Lyophilized compositions containing sphingoglycolipid and process for preparing them |
| ES2235324T3 (es) * | 1997-04-10 | 2005-07-01 | Kirin Beer Kabushiki Kaisha | Empleo de a-glicosilceramidas para la obtencion de un agente terapeutico para enfermedades autoinmunes. |
| TW575420B (en) * | 1997-09-22 | 2004-02-11 | Kirin Brewery | Composition for enhancing cellular immunogenicity comprising alpha-glycosylceramides |
| AU2001268564A1 (en) * | 2000-06-22 | 2002-01-02 | The Brigham And Women's Hospital, Inc. | Alpha-glycosylceramides for treating bacterial and fungal infections |
| AU2002327338A1 (en) * | 2001-07-25 | 2003-02-17 | New York University | Use of glycosylceramides as adjuvants for vaccines against infections and cancer |
| US8367623B2 (en) * | 2001-08-16 | 2013-02-05 | Japan As Represented By President Of National Center Of Neurology And Psychiatry | Glycolipid and medicine for autoimmune disease containing the same as active ingredient |
| US8443383B2 (en) * | 2002-05-03 | 2013-05-14 | Time Warner Cable Enterprises Llc | Use of messages in program signal streams by set-top terminals |
| CA2499265A1 (en) * | 2002-09-20 | 2004-04-01 | Kirin Beer Kabushiki Kaisha | Inhibitor of hepatitis c viruses comprising, as the active ingredient, alpha-glycosylceramide |
| EP1611147A4 (en) * | 2003-03-20 | 2007-10-17 | Univ Brigham Young | 6 "amino-6" -DEOXYGALACTOSYLCERAMIDE |
| US7645873B2 (en) | 2003-03-20 | 2010-01-12 | The Scripps Research Institute | 6″-amino-6″-deoxygalactosylceramides |
| US7309015B2 (en) * | 2004-07-14 | 2007-12-18 | Scanbuy, Inc. | Mobile device gateway providing access to instant information |
| US8513008B2 (en) | 2004-10-07 | 2013-08-20 | Argos Therapeutics, Inc. | Mature dendritic cell compositions and methods for culturing same |
| US20080145931A1 (en) | 2004-10-07 | 2008-06-19 | Argos Therapeutics, Inc. | Mature Dendritic Cell Compositions and Methods of Culturing Same |
| US7923013B2 (en) * | 2004-12-28 | 2011-04-12 | The Rockefeller University | Glycolipids and analogues thereof as antigens for NKT cells |
| JP5090928B2 (ja) * | 2004-12-28 | 2012-12-05 | ザ ロックフェラー ユニバーシティ | Ｎｋｔ細胞に対する抗原としての糖脂質及びその類似体 |
| PT1848813E (pt) | 2005-01-28 | 2013-07-15 | Scripps Research Inst | Activação de glicolípidos bacterianos de células nkt restritas ao cd1d |
| WO2006096500A2 (en) * | 2005-03-04 | 2006-09-14 | The Regents Of The University Of California | Highly efficient synthesis of alpha-o-galactosyl ceramides |
| US20090227781A1 (en) * | 2005-07-01 | 2009-09-10 | Sachiko Miyake | Glycolipid Derivative and Drug Containing the Same as Active Component |
| EP1776963A1 (en) | 2005-10-19 | 2007-04-25 | Gbf-Gesellschaft Für Biotechnologische Forschung Mbh | Hexosylceramides as adjuvants and their uses in pharmaceutical compositions |
| US20070231344A1 (en) * | 2005-10-28 | 2007-10-04 | The Brigham And Women's Hospital, Inc. | Conjugate vaccines for non-proteinaceous antigens |
| PT2056842E (pt) | 2006-04-07 | 2013-01-24 | Univ Chicago | Galactosil-ceramidas modificadas para coloração e estimulação de células t assassinas naturais |
| AU2007269299B2 (en) * | 2006-06-30 | 2013-01-17 | Brigham Young University | Adjuvants and methods of use |
| US8263576B2 (en) * | 2006-08-15 | 2012-09-11 | Mayo Foundation For Medical Education And Research | Non-natural sphingolipid analogs and uses thereof |
| US8916164B2 (en) * | 2007-08-29 | 2014-12-23 | Abivax | Methods of enhancing adjuvaticity of vaccine compositions |
| ES2574825T3 (es) * | 2007-10-12 | 2016-06-22 | Luigi Panza | Análogos de glicolípidos útiles como inmunoadyuvantes |
| EP2058011A1 (en) * | 2007-11-07 | 2009-05-13 | Wittycell | Nkt cell activating gycolipids covalently bound antigens and/or drug |
| US8207135B2 (en) * | 2007-12-05 | 2012-06-26 | Wittycell | Compositions for and methods of enhancing the immune response to antigens |
| CA2739765A1 (en) * | 2008-10-08 | 2010-04-15 | Vincent Serra | Vaccine composition for use against influenza |
| US8378068B2 (en) | 2009-02-16 | 2013-02-19 | Cerenis Therapeutics Holding Sa | Apolipoprotein A-I mimics |
| SG10201708237SA (en) | 2010-10-18 | 2017-11-29 | Cerenis Therapeutics Holding Sa | Compounds, compositions and methods useful for cholesterol mobilisation |
| ES2675582T3 (es) | 2010-12-02 | 2018-07-11 | Riken | Inmunoterapia utilizando células alo-NKT, células para inmunoterapia en las que la cadena alfa del gen del receptor de las células T (TCR) ha sido redistribuida a V alfa-J alfa uniforme, y banco de células NKT derivadas de dichas células |
| US10227290B2 (en) | 2012-02-07 | 2019-03-12 | The Regents Of The University Of California | Glycosphingolipids for use in modulating immune responses |
| AU2013306767A1 (en) | 2012-08-22 | 2015-03-12 | Regimmune Corporation | Preparation for preventing or treating type I diabetes |
| CA2925878A1 (en) | 2012-10-12 | 2014-04-17 | The Brigham And Women's Hospital, Inc. | Glycosphingolipids and methods of use thereof |
| WO2014069655A1 (ja) | 2012-11-05 | 2014-05-08 | 株式会社レグイミューン | 免疫寛容誘導剤 |
| PL2923208T3 (pl) | 2012-11-21 | 2019-09-30 | Institut National De La Santé Et De La Recherche Médicale (Inserm) | Sposoby określania ryzyka ostrej choroby przeszczep przeciwko gospodarzowi |
| JP2015205835A (ja) * | 2014-04-21 | 2015-11-19 | 国立大学法人福井大学 | 中性子線障害防護剤 |
| JPWO2022118913A1 (enExample) | 2020-12-04 | 2022-06-09 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3622666A (en) * | 1968-03-04 | 1971-11-23 | Stanley Drug Products Inc | Methods for treating bacterial infections with phrenosin |
| US4598051A (en) * | 1980-03-12 | 1986-07-01 | The Regents Of The University Of California | Liposome conjugates and diagnostic methods therewith |
| US4806466A (en) * | 1981-10-29 | 1989-02-21 | The Regents Of The University Of California | Cell agglutination reagent comprising conjugates of antibody covalently bound to liposomes |
| IT1168205B (it) * | 1983-07-21 | 1987-05-20 | Wellcome Italia | Derivato di monsialo ganglioside dotato di attivita' antibatterica, antifungina ed antitumorale, composizioni che lo contengono e procedimento per la loro preparazione |
| EP0146810A3 (de) * | 1983-12-05 | 1987-05-13 | Solco Basel AG | Verfahren zur Herstellung von Sphingosinderivaten |
| JPS6157594A (ja) * | 1984-08-30 | 1986-03-24 | Suntory Ltd | ガラクトスフインゴ脂質及びその製造法 |
| DK17885D0 (da) * | 1985-01-14 | 1985-01-14 | Karlsson Karl Anders | Antiviralt middel |
| JPS6239597A (ja) * | 1985-08-13 | 1987-02-20 | ソルコ バ−ゼル アクチエンゲゼルシヤフト | スフインゴシン誘導体の製造方法 |
| JPH07116209B2 (ja) * | 1986-04-11 | 1995-12-13 | メクト株式会社 | シアロシルセラミド類及びその製造方法 |
| US4990603A (en) * | 1986-07-04 | 1991-02-05 | Mect Corporation | Sialic acid derivatives and process therefor |
| US4937232A (en) * | 1986-09-15 | 1990-06-26 | Duke University | Inhibition of protein kinase C by long-chain bases |
| US4816450A (en) * | 1986-09-15 | 1989-03-28 | Duke University | Inhibition of protein kinase C by long-chain bases |
| JPS6495A (en) * | 1986-12-19 | 1989-01-05 | Tosoh Corp | Alpha-glycosyl ceramide derivative |
| US5026557A (en) * | 1987-09-09 | 1991-06-25 | The Liposome Company, Inc. | Adjuvant composition |
| JP2588729B2 (ja) * | 1987-10-05 | 1997-03-12 | 塩野義製薬株式会社 | スフィンゴシン誘導体 |
| US5041441A (en) * | 1988-04-04 | 1991-08-20 | The Regents Of The University Of Michigan | Method of chemotherapy using 1-phenyl-2-decanoylamino-3-morpholino-1-propanol |
| US5073543A (en) * | 1988-07-21 | 1991-12-17 | G. D. Searle & Co. | Controlled release formulations of trophic factors in ganglioside-lipsome vehicle |
| JP2631532B2 (ja) * | 1988-10-14 | 1997-07-16 | 富士写真フイルム株式会社 | 熱転写受像材料 |
| DE3840044A1 (de) * | 1988-11-27 | 1990-06-07 | Behringwerke Ag | Glykosphingolipide mit kopplungsfaehiger gruppe im sphingoidanteil, ihre herstellung und verwendung |
| IT1235162B (it) * | 1988-12-02 | 1992-06-22 | Fidia Farmaceutici | Derivati di lisosfingolipidi |
| US5028715A (en) * | 1989-02-06 | 1991-07-02 | Southwest Research Institute | Radioprotective agents and their method of manufacture |
| DE69011465T2 (de) * | 1989-09-29 | 1995-03-23 | Ajinomoto Kk | Verwendung von Human-ADF (=Adult T-cell leukemia-derived factor) zur Herstellung von Medikamenten. |
| JP3068910B2 (ja) * | 1990-11-08 | 2000-07-24 | 麒麟麦酒株式会社 | 新規スフィンゴ糖脂質、その製造法および使用 |
| JPH06145189A (ja) * | 1991-01-23 | 1994-05-24 | Kitasato Inst:The | スフィンゴ糖脂質 |
| JP3034650B2 (ja) * | 1991-06-19 | 2000-04-17 | 株式会社ジーシー | 歯質用接着剤 |
| JPH0559081A (ja) * | 1991-08-29 | 1993-03-09 | Kirin Brewery Co Ltd | 新規スフインゴ糖脂質、その製造法および使用 |
| US5780441A (en) * | 1993-04-15 | 1998-07-14 | Kirin Beer Kabushiki Kaisha | Sphingoglycolipid compounds and therapeutic uses thereof |
-
1993
- 1993-07-13 TW TW082105589A patent/TW261533B/zh active
- 1993-07-15 DE DE69330096T patent/DE69330096T2/de not_active Expired - Fee Related
- 1993-07-15 AU AU45835/93A patent/AU684466B2/en not_active Ceased
- 1993-07-15 KR KR1019950700164A patent/KR100277621B1/ko not_active Expired - Fee Related
- 1993-07-15 JP JP06503950A patent/JP3088461B2/ja not_active Expired - Fee Related
- 1993-07-15 EP EP93916170A patent/EP0650732B1/en not_active Expired - Lifetime
- 1993-07-15 WO PCT/JP1993/000984 patent/WO1994002168A1/ja not_active Ceased
- 1993-07-15 AT AT93916170T patent/ATE200224T1/de not_active IP Right Cessation
- 1993-07-15 CA CA002140013A patent/CA2140013C/en not_active Expired - Fee Related
- 1993-07-16 CN CN93116586A patent/CN1084623C/zh not_active Expired - Lifetime
-
1995
- 1995-01-13 FI FI950166A patent/FI950166A7/fi unknown
- 1995-03-17 US US08/406,061 patent/US5767092A/en not_active Expired - Fee Related
-
1997
- 1997-06-23 US US08/880,255 patent/US6017892A/en not_active Expired - Fee Related
-
1998
- 1998-10-28 US US09/181,321 patent/US6071884A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| KR950702431A (ko) | 1995-07-29 |
| DE69330096T2 (de) | 2001-10-18 |
| ATE200224T1 (de) | 2001-04-15 |
| US6017892A (en) | 2000-01-25 |
| DE69330096D1 (de) | 2001-05-10 |
| CN1084623C (zh) | 2002-05-15 |
| FI950166A7 (fi) | 1995-01-31 |
| EP0650732A4 (en) | 1998-04-01 |
| AU4583593A (en) | 1994-02-14 |
| CA2140013A1 (en) | 1994-02-03 |
| TW261533B (enExample) | 1995-11-01 |
| WO1994002168A1 (fr) | 1994-02-03 |
| HK1009937A1 (en) | 1999-09-17 |
| EP0650732A1 (en) | 1995-05-03 |
| KR100277621B1 (ko) | 2001-02-01 |
| FI950166A0 (fi) | 1995-01-13 |
| AU684466B2 (en) | 1997-12-18 |
| JP3088461B2 (ja) | 2000-09-18 |
| CN1088093A (zh) | 1994-06-22 |
| EP0650732B1 (en) | 2001-04-04 |
| US5767092A (en) | 1998-06-16 |
| US6071884A (en) | 2000-06-06 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |