OA10096A - Improvements in or relating to contrast agents - Google Patents
Improvements in or relating to contrast agents Download PDFInfo
- Publication number
- OA10096A OA10096A OA60556A OA60556A OA10096A OA 10096 A OA10096 A OA 10096A OA 60556 A OA60556 A OA 60556A OA 60556 A OA60556 A OA 60556A OA 10096 A OA10096 A OA 10096A
- Authority
- OA
- OAPI
- Prior art keywords
- polymer
- contrast agent
- mmol
- solution
- added
- Prior art date
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- 239000002872 contrast media Substances 0.000 title claims abstract description 37
- 229920000642 polymer Polymers 0.000 claims abstract description 166
- 239000011859 microparticle Substances 0.000 claims abstract description 35
- 239000007789 gas Substances 0.000 claims abstract description 22
- 125000000962 organic group Chemical group 0.000 claims abstract description 11
- 238000003384 imaging method Methods 0.000 claims abstract description 10
- 239000001257 hydrogen Substances 0.000 claims abstract description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 238000002604 ultrasonography Methods 0.000 claims abstract description 3
- -1 oxy, carbonyl,oxycarbonyl Chemical group 0.000 claims description 43
- 238000000034 method Methods 0.000 claims description 36
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 9
- 229920001400 block copolymer Polymers 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 7
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 5
- 150000004676 glycans Chemical class 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims description 5
- 229920001282 polysaccharide Polymers 0.000 claims description 5
- 239000005017 polysaccharide Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 229920006037 cross link polymer Polymers 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 229920003169 water-soluble polymer Polymers 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004450 alkenylene group Chemical group 0.000 claims description 3
- 238000002059 diagnostic imaging Methods 0.000 claims description 3
- 229920000578 graft copolymer Polymers 0.000 claims description 3
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 3
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 3
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 2
- 230000005291 magnetic effect Effects 0.000 claims description 2
- SGPGESCZOCHFCL-UHFFFAOYSA-N Tilisolol hydrochloride Chemical compound [Cl-].C1=CC=C2C(=O)N(C)C=C(OCC(O)C[NH2+]C(C)(C)C)C2=C1 SGPGESCZOCHFCL-UHFFFAOYSA-N 0.000 claims 3
- 238000010348 incorporation Methods 0.000 claims 1
- 229920002988 biodegradable polymer Polymers 0.000 abstract 1
- 239000004621 biodegradable polymer Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 123
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 82
- 239000002904 solvent Substances 0.000 description 59
- 239000002245 particle Substances 0.000 description 58
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 55
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 54
- 239000000203 mixture Substances 0.000 description 52
- 238000005481 NMR spectroscopy Methods 0.000 description 51
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- 230000002829 reductive effect Effects 0.000 description 51
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 47
- 239000000047 product Substances 0.000 description 46
- 238000001542 size-exclusion chromatography Methods 0.000 description 45
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 39
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 38
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- 238000003756 stirring Methods 0.000 description 30
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 239000000843 powder Substances 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- 150000001875 compounds Chemical class 0.000 description 23
- 238000000386 microscopy Methods 0.000 description 23
- 101150041968 CDC13 gene Proteins 0.000 description 22
- 230000015572 biosynthetic process Effects 0.000 description 22
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 21
- 229960002415 trichloroethylene Drugs 0.000 description 21
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 21
- PWAXUOGZOSVGBO-UHFFFAOYSA-N adipoyl chloride Chemical compound ClC(=O)CCCCC(Cl)=O PWAXUOGZOSVGBO-UHFFFAOYSA-N 0.000 description 20
- 238000003818 flash chromatography Methods 0.000 description 20
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 19
- 235000019256 formaldehyde Nutrition 0.000 description 19
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- 229920001993 poloxamer 188 Polymers 0.000 description 18
- 239000008096 xylene Substances 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 16
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 239000012074 organic phase Substances 0.000 description 15
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
- 239000002253 acid Substances 0.000 description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 13
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 12
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 229920006395 saturated elastomer Polymers 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 11
- CVASMYWHWRNWOX-UHFFFAOYSA-N chloro methyl carbonate Chemical compound COC(=O)OCl CVASMYWHWRNWOX-UHFFFAOYSA-N 0.000 description 11
- 238000000113 differential scanning calorimetry Methods 0.000 description 11
- 229940073584 methylene chloride Drugs 0.000 description 11
- KGRVJHAUYBGFFP-UHFFFAOYSA-N 2,2'-Methylenebis(4-methyl-6-tert-butylphenol) Chemical compound CC(C)(C)C1=CC(C)=CC(CC=2C(=C(C=C(C)C=2)C(C)(C)C)O)=C1O KGRVJHAUYBGFFP-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
- 239000007788 liquid Substances 0.000 description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 10
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 238000004132 cross linking Methods 0.000 description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 9
- 150000003254 radicals Chemical class 0.000 description 9
- 239000000377 silicon dioxide Substances 0.000 description 9
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 8
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 8
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 229940050390 benzoate Drugs 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 8
- 229940093499 ethyl acetate Drugs 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 239000011591 potassium Substances 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 229960001866 silicon dioxide Drugs 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 108090000371 Esterases Proteins 0.000 description 7
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 7
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 7
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000003153 chemical reaction reagent Substances 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 238000004619 light microscopy Methods 0.000 description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 6
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 6
- 235000011130 ammonium sulphate Nutrition 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 150000005690 diesters Chemical group 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 229920001983 poloxamer Polymers 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- ROHDFQIHKSIGQR-UHFFFAOYSA-N 12-hydroxydodecanoyloxymethyl 12-hydroxydodecanoate Chemical compound OCCCCCCCCCCCC(=O)OCOC(=O)CCCCCCCCCCCO ROHDFQIHKSIGQR-UHFFFAOYSA-N 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 5
- 239000004952 Polyamide Substances 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 5
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 5
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 229920001577 copolymer Polymers 0.000 description 5
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 229920002647 polyamide Polymers 0.000 description 5
- 229920000728 polyester Polymers 0.000 description 5
- 229920001184 polypeptide Polymers 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 5
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-UHFFFAOYSA-N 0.000 description 4
- XGBWPNLUAPNTAD-UHFFFAOYSA-N 10-hydroxydecanoyloxymethyl 10-hydroxydecanoate Chemical compound OCCCCCCCCCC(=O)OCOC(=O)CCCCCCCCCO XGBWPNLUAPNTAD-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000001569 carbon dioxide Substances 0.000 description 4
- 229910002092 carbon dioxide Inorganic materials 0.000 description 4
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 4
- 230000003197 catalytic effect Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 4
- LRUDDHYVRFQYCN-UHFFFAOYSA-L dipotassium;terephthalate Chemical compound [K+].[K+].[O-]C(=O)C1=CC=C(C([O-])=O)C=C1 LRUDDHYVRFQYCN-UHFFFAOYSA-L 0.000 description 4
- 239000002961 echo contrast media Substances 0.000 description 4
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
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- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical class CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 4
- BDJRBEYXGGNYIS-UHFFFAOYSA-N nonanedioic acid Chemical compound OC(=O)CCCCCCCC(O)=O BDJRBEYXGGNYIS-UHFFFAOYSA-N 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
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- 229920001308 poly(aminoacid) Polymers 0.000 description 4
- RWPGFSMJFRPDDP-UHFFFAOYSA-L potassium metabisulfite Chemical compound [K+].[K+].[O-]S(=O)S([O-])(=O)=O RWPGFSMJFRPDDP-UHFFFAOYSA-L 0.000 description 4
- 239000004297 potassium metabisulphite Substances 0.000 description 4
- 235000010263 potassium metabisulphite Nutrition 0.000 description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- KKEYFWRCBNTPAC-UHFFFAOYSA-L terephthalate(2-) Chemical compound [O-]C(=O)C1=CC=C(C([O-])=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-L 0.000 description 4
- GALGFDDHBGDRFQ-UHFFFAOYSA-N 1-ethoxycarbonyloxyethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)OC(C)OC(=O)C(C)=C GALGFDDHBGDRFQ-UHFFFAOYSA-N 0.000 description 3
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 3
- UGAGPNKCDRTDHP-UHFFFAOYSA-N 16-hydroxyhexadecanoic acid Chemical compound OCCCCCCCCCCCCCCCC(O)=O UGAGPNKCDRTDHP-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000004159 Potassium persulphate Substances 0.000 description 3
- 230000002009 allergenic effect Effects 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 3
- MLXKRQZNBPENEJ-UHFFFAOYSA-N chloromethyl hydrogen carbonate Chemical class OC(=O)OCCl MLXKRQZNBPENEJ-UHFFFAOYSA-N 0.000 description 3
- 238000000576 coating method Methods 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/06—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations
- A61K49/18—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes
- A61K49/1818—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles
- A61K49/1821—Nuclear magnetic resonance [NMR] contrast preparations; Magnetic resonance imaging [MRI] contrast preparations characterised by a special physical form, e.g. emulsions, microcapsules, liposomes particles, e.g. uncoated or non-functionalised microparticles or nanoparticles coated or functionalised microparticles or nanoparticles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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GB929204918A GB9204918D0 (en) | 1992-03-06 | 1992-03-06 | Chemical compounds |
GB929204920A GB9204920D0 (en) | 1992-03-06 | 1992-03-06 | Improvements in or relating to contrast agents |
Publications (1)
Publication Number | Publication Date |
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OA10096A true OA10096A (en) | 1996-12-18 |
Family
ID=26300446
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
OA60556A OA10096A (en) | 1992-03-06 | 1994-08-24 | Improvements in or relating to contrast agents |
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Country | Link |
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US (1) | US5795562A (fr) |
EP (1) | EP0627942B1 (fr) |
JP (1) | JP3650393B2 (fr) |
CN (1) | CN1084410A (fr) |
AT (1) | ATE184491T1 (fr) |
AU (1) | AU676467B2 (fr) |
BG (1) | BG99072A (fr) |
BR (1) | BR9306044A (fr) |
CA (1) | CA2130670A1 (fr) |
CZ (1) | CZ284844B6 (fr) |
DE (1) | DE69326447T2 (fr) |
EE (1) | EE03079B1 (fr) |
ES (1) | ES2135466T3 (fr) |
FI (1) | FI944077A0 (fr) |
HU (1) | HUT68612A (fr) |
IL (1) | IL104963A (fr) |
LV (1) | LV10396B (fr) |
NO (1) | NO943272D0 (fr) |
NZ (1) | NZ249548A (fr) |
OA (1) | OA10096A (fr) |
PL (1) | PL174114B1 (fr) |
RU (1) | RU2122432C1 (fr) |
SG (1) | SG44668A1 (fr) |
SK (1) | SK106694A3 (fr) |
WO (1) | WO1993017718A1 (fr) |
Families Citing this family (76)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5922304A (en) * | 1989-12-22 | 1999-07-13 | Imarx Pharmaceutical Corp. | Gaseous precursor filled microspheres as magnetic resonance imaging contrast agents |
IN172208B (fr) * | 1990-04-02 | 1993-05-01 | Sint Sa | |
GB9106686D0 (en) * | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
US5205290A (en) * | 1991-04-05 | 1993-04-27 | Unger Evan C | Low density microspheres and their use as contrast agents for computed tomography |
MX9205298A (es) * | 1991-09-17 | 1993-05-01 | Steven Carl Quay | Medios gaseosos de contraste de ultrasonido y metodo para seleccionar gases para usarse como medios de contraste de ultrasonido |
US5409688A (en) * | 1991-09-17 | 1995-04-25 | Sonus Pharmaceuticals, Inc. | Gaseous ultrasound contrast media |
US6383470B1 (en) | 1992-09-26 | 2002-05-07 | Thomas Fritzsch | Microparticle preparations made of biodegradable copolymers |
IL108416A (en) | 1993-01-25 | 1998-10-30 | Sonus Pharma Inc | Colloids with phase difference as contrast ultrasound agents |
US5558855A (en) * | 1993-01-25 | 1996-09-24 | Sonus Pharmaceuticals | Phase shift colloids as ultrasound contrast agents |
CZ191695A3 (en) * | 1993-01-25 | 1996-05-15 | Sonus Pharma Inc | Biologically compatible contrast agent, process of its preparation and representation method by ultrasound |
GB9305351D0 (en) * | 1993-03-16 | 1993-05-05 | Nycomed Imaging As | Improvements in or relating to contrast agents |
GB9318288D0 (en) * | 1993-09-03 | 1993-10-20 | Nycomed Imaging As | Improvements in or relating to contrast agents |
HU225495B1 (en) | 1993-12-15 | 2007-01-29 | Bracco Research Sa | Gas mixtures useful as ultrasound contrast media |
GB9402867D0 (en) * | 1994-02-15 | 1994-04-06 | Nycomed Imaging As | Improvements in or relating to contrast agents |
GB9417941D0 (en) * | 1994-09-06 | 1994-10-26 | Nycomed Imaging As | Improvements in or relating to contrast agents |
GB9622711D0 (en) * | 1996-10-31 | 1997-01-08 | British Tech Group | Instrument having enhanced ultrasound visibility |
US20020159951A1 (en) * | 1997-05-06 | 2002-10-31 | Unger Evan C. | Novel targeted compositions for diagnostic and therapeutic use |
US7637948B2 (en) | 1997-10-10 | 2009-12-29 | Senorx, Inc. | Tissue marking implant |
US8668737B2 (en) | 1997-10-10 | 2014-03-11 | Senorx, Inc. | Tissue marking implant |
US20010003580A1 (en) | 1998-01-14 | 2001-06-14 | Poh K. Hui | Preparation of a lipid blend and a phospholipid suspension containing the lipid blend |
US6347241B2 (en) | 1999-02-02 | 2002-02-12 | Senorx, Inc. | Ultrasonic and x-ray detectable biopsy site marker and apparatus for applying it |
US6725083B1 (en) | 1999-02-02 | 2004-04-20 | Senorx, Inc. | Tissue site markers for in VIVO imaging |
US8498693B2 (en) | 1999-02-02 | 2013-07-30 | Senorx, Inc. | Intracorporeal marker and marker delivery device |
US6862470B2 (en) | 1999-02-02 | 2005-03-01 | Senorx, Inc. | Cavity-filling biopsy site markers |
US7983734B2 (en) | 2003-05-23 | 2011-07-19 | Senorx, Inc. | Fibrous marker and intracorporeal delivery thereof |
US20090030309A1 (en) | 2007-07-26 | 2009-01-29 | Senorx, Inc. | Deployment of polysaccharide markers |
US7651505B2 (en) | 2002-06-17 | 2010-01-26 | Senorx, Inc. | Plugged tip delivery for marker placement |
US8361082B2 (en) | 1999-02-02 | 2013-01-29 | Senorx, Inc. | Marker delivery device with releasable plug |
US9820824B2 (en) | 1999-02-02 | 2017-11-21 | Senorx, Inc. | Deployment of polysaccharide markers for treating a site within a patent |
US6575991B1 (en) | 1999-06-17 | 2003-06-10 | Inrad, Inc. | Apparatus for the percutaneous marking of a lesion |
US7311893B2 (en) * | 2000-07-25 | 2007-12-25 | Neurochem (International) Limited | Amyloid targeting imaging agents and uses thereof |
EP2319449B1 (fr) | 2000-11-20 | 2016-03-09 | Senorx, Inc. | Marqueurs de sites tissulaires pour l' imagerie in vivo |
GB0128052D0 (en) | 2001-11-22 | 2002-01-16 | Drug Discovery Lab As | Compounds |
AUPR951501A0 (en) * | 2001-12-14 | 2002-01-24 | Smart Drug Systems Inc | Modified sustained release pharmaceutical system |
US7462366B2 (en) | 2002-03-29 | 2008-12-09 | Boston Scientific Scimed, Inc. | Drug delivery particle |
DE10224352A1 (de) * | 2002-06-01 | 2003-12-11 | Mueller Schulte Detlef | Thermosensitive Polymerträger mit veränderbarer physikalischer Struktur für die biochemische Analytik, Diagnostik und Therapie |
WO2003105917A2 (fr) | 2002-06-12 | 2003-12-24 | Scimed Life Systems, Inc. | Agents gonflants |
US7842377B2 (en) | 2003-08-08 | 2010-11-30 | Boston Scientific Scimed, Inc. | Porous polymeric particle comprising polyvinyl alcohol and having interior to surface porosity-gradient |
US8012454B2 (en) | 2002-08-30 | 2011-09-06 | Boston Scientific Scimed, Inc. | Embolization |
US7883490B2 (en) | 2002-10-23 | 2011-02-08 | Boston Scientific Scimed, Inc. | Mixing and delivery of therapeutic compositions |
US20060036158A1 (en) | 2003-11-17 | 2006-02-16 | Inrad, Inc. | Self-contained, self-piercing, side-expelling marking apparatus |
US7877133B2 (en) | 2003-05-23 | 2011-01-25 | Senorx, Inc. | Marker or filler forming fluid |
US7976823B2 (en) | 2003-08-29 | 2011-07-12 | Boston Scientific Scimed, Inc. | Ferromagnetic particles and methods |
US20050273002A1 (en) | 2004-06-04 | 2005-12-08 | Goosen Ryan L | Multi-mode imaging marker |
WO2005061088A1 (fr) * | 2003-12-22 | 2005-07-07 | Finlay Warren H | Fomation de poudre par lyophilisation par vaporisation atmospherique |
US7025726B2 (en) | 2004-01-22 | 2006-04-11 | The Regents Of The University Of Nebraska | Detection of endothelial dysfunction by ultrasonic imaging |
US7736671B2 (en) | 2004-03-02 | 2010-06-15 | Boston Scientific Scimed, Inc. | Embolization |
US8173176B2 (en) | 2004-03-30 | 2012-05-08 | Boston Scientific Scimed, Inc. | Embolization |
US7311861B2 (en) | 2004-06-01 | 2007-12-25 | Boston Scientific Scimed, Inc. | Embolization |
US8425550B2 (en) | 2004-12-01 | 2013-04-23 | Boston Scientific Scimed, Inc. | Embolic coils |
US7727555B2 (en) | 2005-03-02 | 2010-06-01 | Boston Scientific Scimed, Inc. | Particles |
US7858183B2 (en) | 2005-03-02 | 2010-12-28 | Boston Scientific Scimed, Inc. | Particles |
US10357328B2 (en) | 2005-04-20 | 2019-07-23 | Bard Peripheral Vascular, Inc. and Bard Shannon Limited | Marking device with retractable cannula |
US7963287B2 (en) | 2005-04-28 | 2011-06-21 | Boston Scientific Scimed, Inc. | Tissue-treatment methods |
JP2006327986A (ja) * | 2005-05-26 | 2006-12-07 | Nitto Denko Corp | カーボネート基含有(メタ)アクリル酸エステルモノマーとその製造方法 |
US8123693B2 (en) | 2005-06-20 | 2012-02-28 | Conceptus, Inc. | Methods and devices for determining lumen occlusion |
US9463426B2 (en) | 2005-06-24 | 2016-10-11 | Boston Scientific Scimed, Inc. | Methods and systems for coating particles |
US8052658B2 (en) | 2005-10-07 | 2011-11-08 | Bard Peripheral Vascular, Inc. | Drug-eluting tissue marker |
US8007509B2 (en) | 2005-10-12 | 2011-08-30 | Boston Scientific Scimed, Inc. | Coil assemblies, components and methods |
US8152839B2 (en) | 2005-12-19 | 2012-04-10 | Boston Scientific Scimed, Inc. | Embolic coils |
US8101197B2 (en) | 2005-12-19 | 2012-01-24 | Stryker Corporation | Forming coils |
US7947368B2 (en) | 2005-12-21 | 2011-05-24 | Boston Scientific Scimed, Inc. | Block copolymer particles |
EP2079385B1 (fr) | 2006-10-23 | 2013-11-20 | C.R.Bard, Inc. | Marqueur mammaire |
US8414927B2 (en) | 2006-11-03 | 2013-04-09 | Boston Scientific Scimed, Inc. | Cross-linked polymer particles |
EP2109409B1 (fr) | 2006-12-12 | 2018-09-05 | C.R.Bard, Inc. | Marqueur tissulaire pour mode d'imagerie multiple |
US8401622B2 (en) | 2006-12-18 | 2013-03-19 | C. R. Bard, Inc. | Biopsy marker with in situ-generated imaging properties |
WO2009099767A2 (fr) | 2008-01-31 | 2009-08-13 | C.R. Bard, Inc. | Marqueur de tissu pour biopsie |
US9327061B2 (en) | 2008-09-23 | 2016-05-03 | Senorx, Inc. | Porous bioabsorbable implant |
US8670818B2 (en) | 2008-12-30 | 2014-03-11 | C. R. Bard, Inc. | Marker delivery device for tissue marker placement |
US8585616B2 (en) | 2009-10-09 | 2013-11-19 | Conceptus, Inc. | Methods and apparatus for determining fallopian tube occlusion |
USD715942S1 (en) | 2013-09-24 | 2014-10-21 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD716450S1 (en) | 2013-09-24 | 2014-10-28 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD716451S1 (en) | 2013-09-24 | 2014-10-28 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
USD715442S1 (en) | 2013-09-24 | 2014-10-14 | C. R. Bard, Inc. | Tissue marker for intracorporeal site identification |
CN104817662B (zh) * | 2015-04-09 | 2017-07-14 | 清华大学 | 同时用于ct和核磁成像的含碘、含氟氨基磷酸酯类高分子造影剂及其制备方法与应用 |
JP7115914B2 (ja) | 2017-06-23 | 2022-08-09 | 住友化学株式会社 | レジスト組成物及びレジストパターンの製造方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU636481B2 (en) * | 1990-05-18 | 1993-04-29 | Bracco International B.V. | Polymeric gas or air filled microballoons usable as suspensions in liquid carriers for ultrasonic echography |
PH31064A (en) * | 1990-09-07 | 1998-02-05 | Nycomed As Of Nycoveten | Polymers containing diester units. |
GB9106686D0 (en) * | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
GB9106673D0 (en) * | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
US5558857A (en) * | 1991-06-03 | 1996-09-24 | Nycomed Imaging As | Contrast agents |
-
1993
- 1993-03-05 HU HU9402565A patent/HUT68612A/hu unknown
- 1993-03-05 AT AT93905527T patent/ATE184491T1/de active
- 1993-03-05 CZ CZ942148A patent/CZ284844B6/cs not_active IP Right Cessation
- 1993-03-05 EP EP93905527A patent/EP0627942B1/fr not_active Expired - Lifetime
- 1993-03-05 IL IL104963A patent/IL104963A/xx not_active IP Right Cessation
- 1993-03-05 SG SG1996005321A patent/SG44668A1/en unknown
- 1993-03-05 CA CA002130670A patent/CA2130670A1/fr not_active Abandoned
- 1993-03-05 BR BR9306044A patent/BR9306044A/pt not_active Application Discontinuation
- 1993-03-05 SK SK1066-94A patent/SK106694A3/sk unknown
- 1993-03-05 WO PCT/GB1993/000470 patent/WO1993017718A1/fr active IP Right Grant
- 1993-03-05 RU RU94045927A patent/RU2122432C1/ru active
- 1993-03-05 AU AU36424/93A patent/AU676467B2/en not_active Ceased
- 1993-03-05 PL PL93305025A patent/PL174114B1/pl unknown
- 1993-03-05 CN CN93104052A patent/CN1084410A/zh active Pending
- 1993-03-05 DE DE69326447T patent/DE69326447T2/de not_active Expired - Fee Related
- 1993-03-05 LV LVP-93-171A patent/LV10396B/en unknown
- 1993-03-05 JP JP51546493A patent/JP3650393B2/ja not_active Expired - Fee Related
- 1993-03-05 ES ES93905527T patent/ES2135466T3/es not_active Expired - Lifetime
- 1993-03-05 NZ NZ249548A patent/NZ249548A/en unknown
- 1993-03-05 US US08/284,464 patent/US5795562A/en not_active Expired - Fee Related
-
1994
- 1994-05-23 EE EE9400024A patent/EE03079B1/xx unknown
- 1994-08-24 OA OA60556A patent/OA10096A/en unknown
- 1994-09-05 FI FI944077A patent/FI944077A0/fi unknown
- 1994-09-05 NO NO943272A patent/NO943272D0/no not_active Application Discontinuation
- 1994-09-28 BG BG99072A patent/BG99072A/bg unknown
Also Published As
Publication number | Publication date |
---|---|
CN1084410A (zh) | 1994-03-30 |
EP0627942B1 (fr) | 1999-09-15 |
WO1993017718A1 (fr) | 1993-09-16 |
EP0627942A1 (fr) | 1994-12-14 |
IL104963A0 (en) | 1993-07-08 |
JPH07505148A (ja) | 1995-06-08 |
CZ284844B6 (cs) | 1999-03-17 |
RU2122432C1 (ru) | 1998-11-27 |
HUT68612A (en) | 1995-07-28 |
DE69326447D1 (de) | 1999-10-21 |
SG44668A1 (en) | 1997-12-19 |
BR9306044A (pt) | 1997-11-18 |
AU676467B2 (en) | 1997-03-13 |
LV10396B (en) | 1996-02-20 |
EE03079B1 (et) | 1998-04-15 |
CZ214894A3 (en) | 1995-04-12 |
IL104963A (en) | 1997-09-30 |
HU9402565D0 (en) | 1994-11-28 |
NO943272L (no) | 1994-09-05 |
JP3650393B2 (ja) | 2005-05-18 |
NZ249548A (en) | 1996-08-27 |
NO943272D0 (no) | 1994-09-05 |
SK106694A3 (en) | 1995-08-09 |
PL174114B1 (pl) | 1998-06-30 |
US5795562A (en) | 1998-08-18 |
ES2135466T3 (es) | 1999-11-01 |
BG99072A (bg) | 1995-09-29 |
FI944077A (fi) | 1994-09-05 |
RU94045927A (ru) | 1996-11-10 |
DE69326447T2 (de) | 2000-05-18 |
LV10396A (lv) | 1995-02-20 |
CA2130670A1 (fr) | 1993-09-07 |
ATE184491T1 (de) | 1999-10-15 |
AU3642493A (en) | 1993-10-05 |
FI944077A0 (fi) | 1994-09-05 |
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