LT3216B - Contrast agent - Google Patents
Contrast agent Download PDFInfo
- Publication number
- LT3216B LT3216B LTIP391A LTIP391A LT3216B LT 3216 B LT3216 B LT 3216B LT IP391 A LTIP391 A LT IP391A LT IP391 A LTIP391 A LT IP391A LT 3216 B LT3216 B LT 3216B
- Authority
- LT
- Lithuania
- Prior art keywords
- polymer
- contrast agent
- mmol
- added
- group
- Prior art date
Links
- 239000002872 contrast media Substances 0.000 title claims description 36
- 229920000642 polymer Polymers 0.000 claims abstract description 227
- 125000000962 organic group Chemical group 0.000 claims abstract description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims abstract description 12
- 229920001184 polypeptide Polymers 0.000 claims abstract description 10
- 102000004196 processed proteins & peptides Human genes 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- 229920003169 water-soluble polymer Polymers 0.000 claims abstract description 5
- -1 oxy, carbonyl Chemical group 0.000 claims description 52
- 239000011859 microparticle Substances 0.000 claims description 37
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 239000007789 gas Substances 0.000 claims description 26
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 9
- 239000005977 Ethylene Substances 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000001931 aliphatic group Chemical group 0.000 claims description 7
- 229920001400 block copolymer Polymers 0.000 claims description 7
- 229920001577 copolymer Polymers 0.000 claims description 7
- 150000004676 glycans Chemical class 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229920001282 polysaccharide Polymers 0.000 claims description 7
- 239000005017 polysaccharide Substances 0.000 claims description 7
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000005647 linker group Chemical group 0.000 claims description 5
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- 229920002988 biodegradable polymer Polymers 0.000 claims description 4
- 239000004621 biodegradable polymer Substances 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 238000012285 ultrasound imaging Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-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
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 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
- 125000004429 atom Chemical group 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 2
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 2
- 125000000732 arylene group Chemical group 0.000 claims 1
- 239000000243 solution Substances 0.000 description 118
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 97
- 239000002904 solvent Substances 0.000 description 71
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 68
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 65
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
- 239000002245 particle Substances 0.000 description 61
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 60
- 239000011541 reaction mixture Substances 0.000 description 59
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 230000015572 biosynthetic process Effects 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- 239000000047 product Substances 0.000 description 36
- 150000001875 compounds Chemical class 0.000 description 34
- 238000000034 method Methods 0.000 description 32
- 238000000386 microscopy Methods 0.000 description 31
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 239000000839 emulsion Substances 0.000 description 29
- 239000000843 powder Substances 0.000 description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 23
- XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 23
- 238000004587 chromatography analysis Methods 0.000 description 23
- 238000003818 flash chromatography Methods 0.000 description 23
- 239000002808 molecular sieve Substances 0.000 description 23
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 229920001993 poloxamer 188 Polymers 0.000 description 22
- PWAXUOGZOSVGBO-UHFFFAOYSA-N adipoyl chloride Chemical compound ClC(=O)CCCCC(Cl)=O PWAXUOGZOSVGBO-UHFFFAOYSA-N 0.000 description 21
- 239000000725 suspension Substances 0.000 description 21
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000008096 xylene Substances 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 18
- 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 17
- 239000012074 organic phase Substances 0.000 description 17
- 238000006116 polymerization reaction Methods 0.000 description 16
- RGPYVAUWRFGVHX-UHFFFAOYSA-N 1-[1-(2-methylprop-2-enoylamino)propan-2-yloxycarbonyloxy]ethyl acetate Chemical compound CC(=C)C(=O)NCC(C)OC(=O)OC(C)OC(C)=O RGPYVAUWRFGVHX-UHFFFAOYSA-N 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- HKYFLUZPQFOABT-UHFFFAOYSA-N 16-hydroxyhexadecanoyloxymethyl 16-hydroxyhexadecanoate Chemical compound OCCCCCCCCCCCCCCCC(=O)OCOC(=O)CCCCCCCCCCCCCCCO HKYFLUZPQFOABT-UHFFFAOYSA-N 0.000 description 14
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical compound C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000004132 cross linking Methods 0.000 description 14
- 239000000463 material Substances 0.000 description 14
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- CVASMYWHWRNWOX-UHFFFAOYSA-N chloro methyl carbonate Chemical compound COC(=O)OCl CVASMYWHWRNWOX-UHFFFAOYSA-N 0.000 description 13
- OKPYIWASQZGASP-UHFFFAOYSA-N n-(2-hydroxypropyl)-2-methylprop-2-enamide Chemical compound CC(O)CNC(=O)C(C)=C OKPYIWASQZGASP-UHFFFAOYSA-N 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- 229920006395 saturated elastomer Polymers 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 239000012299 nitrogen atmosphere Substances 0.000 description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 description 11
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
- ROHDFQIHKSIGQR-UHFFFAOYSA-N 12-hydroxydodecanoyloxymethyl 12-hydroxydodecanoate Chemical compound OCCCCCCCCCCCC(=O)OCOC(=O)CCCCCCCCCCCO ROHDFQIHKSIGQR-UHFFFAOYSA-N 0.000 description 10
- 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 10
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 10
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 10
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 10
- JPCDQCQGUMTOBH-UHFFFAOYSA-N chloromethyl ethylsulfanylformate Chemical compound CCSC(=O)OCCl JPCDQCQGUMTOBH-UHFFFAOYSA-N 0.000 description 10
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 10
- 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 9
- XGBWPNLUAPNTAD-UHFFFAOYSA-N 10-hydroxydecanoyloxymethyl 10-hydroxydecanoate Chemical compound OCCCCCCCCCC(=O)OCOC(=O)CCCCCCCCCO XGBWPNLUAPNTAD-UHFFFAOYSA-N 0.000 description 9
- FDIHYONBFVCOPU-UHFFFAOYSA-N 2-methylprop-2-enoyloxymethyl benzoate Chemical compound CC(=C)C(=O)OCOC(=O)C1=CC=CC=C1 FDIHYONBFVCOPU-UHFFFAOYSA-N 0.000 description 9
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 9
- 108090000371 Esterases Proteins 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 9
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 9
- 229940039231 contrast media Drugs 0.000 description 9
- HQPMKSGTIOYHJT-UHFFFAOYSA-N ethane-1,2-diol;propane-1,2-diol Chemical compound OCCO.CC(O)CO HQPMKSGTIOYHJT-UHFFFAOYSA-N 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 102000008100 Human Serum Albumin Human genes 0.000 description 8
- 108091006905 Human Serum Albumin Proteins 0.000 description 8
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 150000005690 diesters Chemical group 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 239000011780 sodium chloride Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- WAIFIHKBNYUZGZ-UHFFFAOYSA-N 1-(2-methylprop-2-enoylamino)propan-2-yloxycarbonyloxymethyl acetate Chemical compound CC(=C)C(=O)NCC(C)OC(=O)OCOC(C)=O WAIFIHKBNYUZGZ-UHFFFAOYSA-N 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 238000006065 biodegradation reaction Methods 0.000 description 7
- 239000007857 degradation product Substances 0.000 description 7
- 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 7
- 238000001035 drying Methods 0.000 description 7
- 239000003480 eluent Substances 0.000 description 7
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- HRBNXCSWUDHDLM-UHFFFAOYSA-N 1-methoxycarbonyloxyethyl 2-methylprop-2-enoate Chemical compound COC(=O)OC(C)OC(=O)C(C)=C HRBNXCSWUDHDLM-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 description 6
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 6
- 125000000524 functional group Chemical group 0.000 description 6
- 230000009477 glass transition Effects 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 238000003384 imaging method Methods 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 description 6
- 238000010526 radical polymerization reaction Methods 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- ZHESMCIWZWYNLC-UHFFFAOYSA-N 2-methylprop-2-enoyloxymethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCOC(=O)C(C)=C ZHESMCIWZWYNLC-UHFFFAOYSA-N 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
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 239000001569 carbon dioxide Substances 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 230000003197 catalytic effect Effects 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000003094 microcapsule Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000003960 organic solvent Substances 0.000 description 5
- 229920002647 polyamide Polymers 0.000 description 5
- 229920000728 polyester Polymers 0.000 description 5
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 5
- LLLCSBYSPJHDJX-UHFFFAOYSA-M potassium;2-methylprop-2-enoate Chemical compound [K+].CC(=C)C([O-])=O LLLCSBYSPJHDJX-UHFFFAOYSA-M 0.000 description 5
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 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
- QPFMBZIOSGYJDE-UHFFFAOYSA-N 1,1,2,2-tetrachloroethane Chemical compound ClC(Cl)C(Cl)Cl QPFMBZIOSGYJDE-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
- SGNWYBYMEXVLPE-UHFFFAOYSA-N CCOC(=O)OCOOC(=O)C(=C)C Chemical compound CCOC(=O)OCOOC(=O)C(=C)C SGNWYBYMEXVLPE-UHFFFAOYSA-N 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- UIRNOIFHMQKWFT-UHFFFAOYSA-N [ethenoxycarbonyloxy(phenyl)methyl] acetate Chemical compound C=COC(=O)OC(OC(=O)C)C1=CC=CC=C1 UIRNOIFHMQKWFT-UHFFFAOYSA-N 0.000 description 4
- 150000001299 aldehydes Chemical class 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- MTEKXDFEGSRPPS-UHFFFAOYSA-N bis(carbonochloridoyloxymethyl) benzene-1,4-dicarboxylate Chemical compound ClC(=O)OCOC(=O)C1=CC=C(C(=O)OCOC(Cl)=O)C=C1 MTEKXDFEGSRPPS-UHFFFAOYSA-N 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- XKYNLGVLGFPYRQ-UHFFFAOYSA-N butoxycarbonyloxymethyl 2-methylprop-2-enoate Chemical compound CCCCOC(=O)OCOC(=O)C(C)=C XKYNLGVLGFPYRQ-UHFFFAOYSA-N 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
- 238000000576 coating method Methods 0.000 description 4
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- NZZFYRREKKOMAT-UHFFFAOYSA-N diiodomethane Chemical compound ICI NZZFYRREKKOMAT-UHFFFAOYSA-N 0.000 description 4
- 239000002961 echo contrast media Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 239000004005 microsphere Substances 0.000 description 4
- 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
- 235000010263 potassium metabisulphite Nutrition 0.000 description 4
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 238000002604 ultrasonography Methods 0.000 description 4
- CERXDWLUWLFFEK-UHFFFAOYSA-N 1-chloroethyl methyl carbonate Chemical compound COC(=O)OC(C)Cl CERXDWLUWLFFEK-UHFFFAOYSA-N 0.000 description 3
- YJCJVMMDTBEITC-UHFFFAOYSA-N 10-hydroxycapric acid Chemical compound OCCCCCCCCCC(O)=O YJCJVMMDTBEITC-UHFFFAOYSA-N 0.000 description 3
- ZDHCZVWCTKTBRY-UHFFFAOYSA-N 12-hydroxylauric acid Chemical compound OCCCCCCCCCCCC(O)=O ZDHCZVWCTKTBRY-UHFFFAOYSA-N 0.000 description 3
- VOWDCCFXULVMDY-UHFFFAOYSA-N 16-trityloxyhexadecanoic acid Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(OCCCCCCCCCCCCCCCC(=O)O)C1=CC=CC=C1 VOWDCCFXULVMDY-UHFFFAOYSA-N 0.000 description 3
- 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 3
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- SEEYHRCMNMPHDG-UHFFFAOYSA-N 2-chloroethyl ethyl carbonate Chemical compound CCOC(=O)OCCCl SEEYHRCMNMPHDG-UHFFFAOYSA-N 0.000 description 3
- 101150065749 Churc1 gene Proteins 0.000 description 3
- 229920002307 Dextran Polymers 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 3
- 102100038239 Protein Churchill Human genes 0.000 description 3
- PDQDJZLOMGSJFK-UHFFFAOYSA-N acetyloxymethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCOC(C)=O PDQDJZLOMGSJFK-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 235000019445 benzyl alcohol Nutrition 0.000 description 3
- MBUCWFHXWNITCQ-UHFFFAOYSA-N butyl chloromethyl carbonate Chemical compound CCCCOC(=O)OCCl MBUCWFHXWNITCQ-UHFFFAOYSA-N 0.000 description 3
- TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical class [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 3
- MULZXZRAWSJCCF-UHFFFAOYSA-N carbonochloridoyloxymethyl acetate Chemical compound CC(=O)OCOC(Cl)=O MULZXZRAWSJCCF-UHFFFAOYSA-N 0.000 description 3
- GHGHDTQEVUBIBQ-UHFFFAOYSA-N carbonochloridoyloxymethyl benzoate Chemical compound ClC(=O)OCOC(=O)C1=CC=CC=C1 GHGHDTQEVUBIBQ-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- QOPVNWQGBQYBBP-UHFFFAOYSA-N chloroethyl chloroformate Chemical compound CC(Cl)OC(Cl)=O QOPVNWQGBQYBBP-UHFFFAOYSA-N 0.000 description 3
- 238000005354 coacervation Methods 0.000 description 3
- 239000011248 coating agent Substances 0.000 description 3
- 238000004440 column chromatography Methods 0.000 description 3
- 238000007334 copolymerization reaction Methods 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000002565 electrocardiography Methods 0.000 description 3
- 238000004945 emulsification Methods 0.000 description 3
- 238000007720 emulsion polymerization reaction Methods 0.000 description 3
- 230000007071 enzymatic hydrolysis Effects 0.000 description 3
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 3
- 125000003700 epoxy group Chemical group 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 150000002430 hydrocarbons Chemical class 0.000 description 3
- 125000001183 hydrocarbyl group Chemical group 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 150000002576 ketones Chemical class 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- FQPSGWSUVKBHSU-UHFFFAOYSA-N methacrylamide Chemical class CC(=C)C(N)=O FQPSGWSUVKBHSU-UHFFFAOYSA-N 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000007764 o/w emulsion Substances 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 229920002401 polyacrylamide Polymers 0.000 description 3
- 238000012667 polymer degradation Methods 0.000 description 3
- 229920002635 polyurethane Polymers 0.000 description 3
- 239000004814 polyurethane Substances 0.000 description 3
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
- 229940043349 potassium metabisulfite Drugs 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000035945 sensitivity Effects 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- MIGZEIZMIDGNJM-UHFFFAOYSA-N 1-chloroethyl decyl carbonate Chemical compound CCCCCCCCCCOC(=O)OC(C)Cl MIGZEIZMIDGNJM-UHFFFAOYSA-N 0.000 description 2
- UGAGPNKCDRTDHP-UHFFFAOYSA-N 16-hydroxyhexadecanoic acid Chemical compound OCCCCCCCCCCCCCCCC(O)=O UGAGPNKCDRTDHP-UHFFFAOYSA-N 0.000 description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 2
- OMIGHNLMNHATMP-UHFFFAOYSA-N 2-hydroxyethyl prop-2-enoate Chemical compound OCCOC(=O)C=C OMIGHNLMNHATMP-UHFFFAOYSA-N 0.000 description 2
- JDTUPLBMGDDPJS-UHFFFAOYSA-N 2-methoxy-2-phenylethanol Chemical compound COC(CO)C1=CC=CC=C1 JDTUPLBMGDDPJS-UHFFFAOYSA-N 0.000 description 2
- FJCWISIZLKGKSG-UHFFFAOYSA-N 2-methylprop-2-enoylperoxymethyl benzoate Chemical compound CC(=C)C(=O)OOCOC(=O)C1=CC=CC=C1 FJCWISIZLKGKSG-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- RNTFGLYZQONQHQ-UHFFFAOYSA-N 8-(1-decoxycarbonyloxyethoxy)-8-oxooctanoic acid Chemical compound CCCCCCCCCCOC(=O)OC(C)OC(=O)CCCCCCC(O)=O RNTFGLYZQONQHQ-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- KALMPSSJLLQUQF-UHFFFAOYSA-N CC(=C)C(=O)OOCOC(=O)OC Chemical compound CC(=C)C(=O)OOCOC(=O)OC KALMPSSJLLQUQF-UHFFFAOYSA-N 0.000 description 2
- ZGHMIFIMPOGYEC-UHFFFAOYSA-N CC(C(OOCOC(O)=O)=O)=C Chemical class CC(C(OOCOC(O)=O)=O)=C ZGHMIFIMPOGYEC-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 239000004908 Emulsion polymer Substances 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 239000004593 Epoxy Substances 0.000 description 2
- UQSXHKLRYXJYBZ-UHFFFAOYSA-N Iron oxide Chemical compound [Fe]=O UQSXHKLRYXJYBZ-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
- 235000010582 Pisum sativum Nutrition 0.000 description 2
- 240000004713 Pisum sativum Species 0.000 description 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 2
- 229920002732 Polyanhydride Polymers 0.000 description 2
- 229920001710 Polyorthoester Polymers 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 229920003081 Povidone K 30 Polymers 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 229920001963 Synthetic biodegradable polymer Polymers 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- ZKFKAQYYRCQEEL-UHFFFAOYSA-N [4-(hydroxymethyl)benzoyl]oxymethyl 4-(hydroxymethyl)benzoate Chemical compound C1=CC(CO)=CC=C1C(=O)OCOC(=O)C1=CC=C(CO)C=C1 ZKFKAQYYRCQEEL-UHFFFAOYSA-N 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 238000004220 aggregation Methods 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 125000003158 alcohol group Chemical group 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- BEPWYFBLGRQFFK-UHFFFAOYSA-N benzyl chloromethyl carbonate Chemical compound ClCOC(=O)OCC1=CC=CC=C1 BEPWYFBLGRQFFK-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- JZSHLHOGUGPDRC-UHFFFAOYSA-N bis(propanethioyloxymethyl) benzene-1,4-dicarboxylate Chemical compound CCC(=S)OCOC(=O)C1=CC=C(C(=O)OCOC(=S)CC)C=C1 JZSHLHOGUGPDRC-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 229910052792 caesium Inorganic materials 0.000 description 2
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 2
- 229910000024 caesium carbonate Inorganic materials 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- WBESUKJKQMKSLM-UHFFFAOYSA-N carbonochloridoyloxymethyl decanoate Chemical compound CCCCCCCCCC(=O)OCOC(Cl)=O WBESUKJKQMKSLM-UHFFFAOYSA-N 0.000 description 2
- WOWHHFRSBJGXCM-UHFFFAOYSA-M cetyltrimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)C WOWHHFRSBJGXCM-UHFFFAOYSA-M 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- DRTIZOYLKCWDKR-UHFFFAOYSA-N chloromethyl 1-(2-methylprop-2-enoylamino)propan-2-yl carbonate Chemical compound CC(=C)C(=O)NCC(C)OC(=O)OCCl DRTIZOYLKCWDKR-UHFFFAOYSA-N 0.000 description 2
- OWXJNOQKRZGRDD-UHFFFAOYSA-N chloromethyl decyl carbonate Chemical compound CCCCCCCCCCOC(=O)OCCl OWXJNOQKRZGRDD-UHFFFAOYSA-N 0.000 description 2
- RTFGZMKXMSDULM-UHFFFAOYSA-N chloromethyl ethyl carbonate Chemical compound CCOC(=O)OCCl RTFGZMKXMSDULM-UHFFFAOYSA-N 0.000 description 2
- MFSHZGFPADYOTO-UHFFFAOYSA-N chloromethyl methyl carbonate Chemical compound COC(=O)OCCl MFSHZGFPADYOTO-UHFFFAOYSA-N 0.000 description 2
- 150000003983 crown ethers Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- BFUWRLFOXRAWGF-UHFFFAOYSA-N ethylsulfanylformic acid Chemical compound CCSC(O)=O BFUWRLFOXRAWGF-UHFFFAOYSA-N 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- NAQMVNRVTILPCV-UHFFFAOYSA-N hexane-1,6-diamine Chemical compound NCCCCCCN NAQMVNRVTILPCV-UHFFFAOYSA-N 0.000 description 2
- 230000003301 hydrolyzing effect Effects 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 238000012690 ionic polymerization Methods 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 125000005395 methacrylic acid group Chemical group 0.000 description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 229920000620 organic polymer Polymers 0.000 description 2
- 210000003101 oviduct Anatomy 0.000 description 2
- 230000033116 oxidation-reduction process Effects 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000004584 polyacrylic acid Substances 0.000 description 2
- 229920000515 polycarbonate Polymers 0.000 description 2
- 239000004417 polycarbonate Substances 0.000 description 2
- 238000012643 polycondensation polymerization Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000000379 polymerizing effect Effects 0.000 description 2
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 description 2
- 229920000136 polysorbate Polymers 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- QDIGBJJRWUZARS-UHFFFAOYSA-M potassium;decanoate Chemical compound [K+].CCCCCCCCCC([O-])=O QDIGBJJRWUZARS-UHFFFAOYSA-M 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- SXYFKXOFMCIXQW-UHFFFAOYSA-N propanedioyl dichloride Chemical compound ClC(=O)CC(Cl)=O SXYFKXOFMCIXQW-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000001384 succinic acid Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- GYSCBCSGKXNZRH-UHFFFAOYSA-N 1-benzothiophene-2-carboxamide Chemical compound C1=CC=C2SC(C(=O)N)=CC2=C1 GYSCBCSGKXNZRH-UHFFFAOYSA-N 0.000 description 1
- WUTXMHXUUCWTQZ-UHFFFAOYSA-N 1-o-benzyl 8-o-(1-decoxycarbonyloxyethyl) octanedioate Chemical compound CCCCCCCCCCOC(=O)OC(C)OC(=O)CCCCCCC(=O)OCC1=CC=CC=C1 WUTXMHXUUCWTQZ-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- 229940114073 10-hydroxydecanoate Drugs 0.000 description 1
- NZFOFZSUISORMH-UHFFFAOYSA-N 16-trityloxyhexadecanoyloxymethyl 16-trityloxyhexadecanoate Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(C=1C=CC=CC=1)OCCCCCCCCCCCCCCCC(=O)OCOC(=O)CCCCCCCCCCCCCCCOC(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 NZFOFZSUISORMH-UHFFFAOYSA-N 0.000 description 1
- ULIKDJVNUXNQHS-UHFFFAOYSA-N 2-Propene-1-thiol Chemical compound SCC=C ULIKDJVNUXNQHS-UHFFFAOYSA-N 0.000 description 1
- ZHGGHNZZJCJQSL-UHFFFAOYSA-N 2-[2-(2-ethoxyethoxy)ethoxymethyl]propanedioic acid Chemical compound CCOCCOCCOCC(C(O)=O)C(O)=O ZHGGHNZZJCJQSL-UHFFFAOYSA-N 0.000 description 1
- SVDDJQGVOFZBNX-UHFFFAOYSA-N 2-chloroethyl carbonochloridate Chemical compound ClCCOC(Cl)=O SVDDJQGVOFZBNX-UHFFFAOYSA-N 0.000 description 1
- VKEIPALYOJMDAC-UHFFFAOYSA-N 3,3,3-trichloroprop-1-ene Chemical compound ClC(Cl)(Cl)C=C VKEIPALYOJMDAC-UHFFFAOYSA-N 0.000 description 1
- ISCMYZGMRHODRP-UHFFFAOYSA-N 3-(iminomethylideneamino)-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCN=C=N ISCMYZGMRHODRP-UHFFFAOYSA-N 0.000 description 1
- KJDDUXULCWSDJR-UHFFFAOYSA-N 3-aminooxy-3-oxopropanoic acid Chemical class NOC(=O)CC(O)=O KJDDUXULCWSDJR-UHFFFAOYSA-N 0.000 description 1
- RGUKYNXWOWSRET-UHFFFAOYSA-N 4-pyrrolidin-1-ylpyridine Chemical compound C1CCCN1C1=CC=NC=C1 RGUKYNXWOWSRET-UHFFFAOYSA-N 0.000 description 1
- 125000002373 5 membered heterocyclic group Chemical group 0.000 description 1
- 125000004070 6 membered heterocyclic group Chemical group 0.000 description 1
- RWQUWTMOHXGTNN-UHFFFAOYSA-N 9-n,10-n-bis(4-butylphenyl)-9-n,10-n-bis(4-methylphenyl)phenanthrene-9,10-diamine Chemical compound C1=CC(CCCC)=CC=C1N(C=1C2=CC=CC=C2C2=CC=CC=C2C=1N(C=1C=CC(C)=CC=1)C=1C=CC(CCCC)=CC=1)C1=CC=C(C)C=C1 RWQUWTMOHXGTNN-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- VKVJIANWWQXASP-UHFFFAOYSA-N CC(=C)C(=O)OOCOC(=O)C Chemical compound CC(=C)C(=O)OOCOC(=O)C VKVJIANWWQXASP-UHFFFAOYSA-N 0.000 description 1
- XGECMPIXGWVAHO-UHFFFAOYSA-N CC(=C)C(=O)OOCOC(=O)OCC1=CC=CC=C1 Chemical compound CC(=C)C(=O)OOCOC(=O)OCC1=CC=CC=C1 XGECMPIXGWVAHO-UHFFFAOYSA-N 0.000 description 1
- UWYPZLXLULLAGE-UHFFFAOYSA-N CCOCCOCCOCC(C(=O)Cl)C(=O)Cl Chemical compound CCOCCOCCOCC(C(=O)Cl)C(=O)Cl UWYPZLXLULLAGE-UHFFFAOYSA-N 0.000 description 1
- 241000700114 Chinchillidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- GHVNFZFCNZKVNT-UHFFFAOYSA-N Decanoic acid Natural products CCCCCCCCCC(O)=O GHVNFZFCNZKVNT-UHFFFAOYSA-N 0.000 description 1
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical class S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 1
- 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 1
- 239000002841 Lewis acid Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910018503 SF6 Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- XJBAEMSUCWGCEM-UHFFFAOYSA-N [chloro(phenyl)methyl] ethenyl carbonate Chemical compound C=COC(=O)OC(Cl)C1=CC=CC=C1 XJBAEMSUCWGCEM-UHFFFAOYSA-N 0.000 description 1
- ZXQYGBMAQZUVMI-QQDHXZELSA-N [cyano-(3-phenoxyphenyl)methyl] (1r,3r)-3-[(z)-2-chloro-3,3,3-trifluoroprop-1-enyl]-2,2-dimethylcyclopropane-1-carboxylate Chemical compound CC1(C)[C@@H](\C=C(/Cl)C(F)(F)F)[C@H]1C(=O)OC(C#N)C1=CC=CC(OC=2C=CC=CC=2)=C1 ZXQYGBMAQZUVMI-QQDHXZELSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003570 air Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000002070 alkenylidene group Chemical group 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- IYABWNGZIDDRAK-UHFFFAOYSA-N allene Chemical group C=C=C IYABWNGZIDDRAK-UHFFFAOYSA-N 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 125000003368 amide group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 239000001099 ammonium carbonate Substances 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 238000006664 bond formation reaction Methods 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- JHIFCBJZDLCWAN-UHFFFAOYSA-N butoxycarbonyloxymethyl prop-2-enoate Chemical compound CCCCOC(=O)OCOC(=O)C=C JHIFCBJZDLCWAN-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000005587 carbonate group Chemical group 0.000 description 1
- 125000005586 carbonic acid group Chemical group 0.000 description 1
- MMCOUVMKNAHQOY-UHFFFAOYSA-N carbonoperoxoic acid Chemical compound OOC(O)=O MMCOUVMKNAHQOY-UHFFFAOYSA-N 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- QVISUHUAVCZFMP-UHFFFAOYSA-N carboxyoxymethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCOC(O)=O QVISUHUAVCZFMP-UHFFFAOYSA-N 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 238000013155 cardiography Methods 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 210000003850 cellular structure Anatomy 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
- SMJYMSAPPGLBAR-UHFFFAOYSA-N chloromethyl acetate Chemical compound CC(=O)OCCl SMJYMSAPPGLBAR-UHFFFAOYSA-N 0.000 description 1
- BOXZXICVMMSYPE-UHFFFAOYSA-N chloromethyl benzoate Chemical compound ClCOC(=O)C1=CC=CC=C1 BOXZXICVMMSYPE-UHFFFAOYSA-N 0.000 description 1
- ZKOFCURZLHKSBQ-UHFFFAOYSA-N chloromethyl ethenyl carbonate Chemical class ClCOC(=O)OC=C ZKOFCURZLHKSBQ-UHFFFAOYSA-N 0.000 description 1
- MLXKRQZNBPENEJ-UHFFFAOYSA-N chloromethyl hydrogen carbonate Chemical class OC(=O)OCCl MLXKRQZNBPENEJ-UHFFFAOYSA-N 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000006356 dehydrogenation reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000000151 deposition Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 229920000359 diblock copolymer Polymers 0.000 description 1
- 125000001142 dicarboxylic acid group Chemical group 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 125000005442 diisocyanate group Chemical group 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- WBZKQQHYRPRKNJ-UHFFFAOYSA-L disulfite Chemical compound [O-]S(=O)S([O-])(=O)=O WBZKQQHYRPRKNJ-UHFFFAOYSA-L 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 101150116409 dys-1 gene Proteins 0.000 description 1
- 238000002592 echocardiography Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 238000010556 emulsion polymerization method Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- PQLFROTZSIMBKR-UHFFFAOYSA-N ethenyl carbonochloridate Chemical compound ClC(=O)OC=C PQLFROTZSIMBKR-UHFFFAOYSA-N 0.000 description 1
- FXPHJTKVWZVEGA-UHFFFAOYSA-N ethenyl hydrogen carbonate Chemical class OC(=O)OC=C FXPHJTKVWZVEGA-UHFFFAOYSA-N 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- MKEVFCHVGWJVEU-UHFFFAOYSA-N ethoxycarbonyloxymethyl 2-methylprop-2-enoate Chemical compound CCOC(=O)OCOC(=O)C(C)=C MKEVFCHVGWJVEU-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- UHMZHYUCMREDRI-UHFFFAOYSA-N ethyl thiohypochlorite Chemical compound CCSCl UHMZHYUCMREDRI-UHFFFAOYSA-N 0.000 description 1
- XSVWMPNFRPYZOW-UHFFFAOYSA-N ethylsulfanylcarbonyloxymethyl acetate Chemical compound CCSC(=O)OCOC(C)=O XSVWMPNFRPYZOW-UHFFFAOYSA-N 0.000 description 1
- JNYPZVFZADBJPD-UHFFFAOYSA-N ethylsulfanylcarbonyloxymethyl benzoate Chemical compound CCSC(=O)OCOC(=O)C1=CC=CC=C1 JNYPZVFZADBJPD-UHFFFAOYSA-N 0.000 description 1
- GZVDWGWLIMTYHX-UHFFFAOYSA-N ethylsulfanylcarbonyloxymethyl decanoate Chemical compound CCCCCCCCCC(=O)OCOC(=O)SCC GZVDWGWLIMTYHX-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 description 1
- 125000003651 hexanedioyl group Chemical group C(CCCCC(=O)*)(=O)* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 150000001261 hydroxy acids Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 210000003111 iliac vein Anatomy 0.000 description 1
- 125000000879 imine group Chemical group 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 239000011147 inorganic material Substances 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000005291 magnetic effect Effects 0.000 description 1
- 125000000346 malonyl group Chemical group C(CC(=O)*)(=O)* 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 150000002734 metacrylic acid derivatives Chemical class 0.000 description 1
- JUALYYGOQNLSOT-UHFFFAOYSA-N methoxycarbonyloxymethyl 2-methylprop-2-enoate Chemical compound COC(=O)OCOC(=O)C(C)=C JUALYYGOQNLSOT-UHFFFAOYSA-N 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 125000003431 oxalo group Chemical group 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000005298 paramagnetic effect Effects 0.000 description 1
- 238000003921 particle size analysis Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 description 1
- TVDCUCKBZCDWRS-UHFFFAOYSA-N phenylmethoxycarbonyloxymethyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCOC(=O)OCC1=CC=CC=C1 TVDCUCKBZCDWRS-UHFFFAOYSA-N 0.000 description 1
- VZCMFZFRZYSIGM-UHFFFAOYSA-N phenylmethoxymethyl carbonochloridate Chemical compound ClC(=O)OCOCC1=CC=CC=C1 VZCMFZFRZYSIGM-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 229960000502 poloxamer Drugs 0.000 description 1
- 229920000771 poly (alkylcyanoacrylate) Polymers 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000004300 potassium benzoate Substances 0.000 description 1
- 235000010235 potassium benzoate Nutrition 0.000 description 1
- 229940103091 potassium benzoate Drugs 0.000 description 1
- 239000004297 potassium metabisulphite Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 210000004777 protein coat Anatomy 0.000 description 1
- 235000021251 pulses Nutrition 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003014 reinforcing effect Effects 0.000 description 1
- 238000001226 reprecipitation Methods 0.000 description 1
- 239000013557 residual solvent Substances 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 238000004621 scanning probe microscopy Methods 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- GGXKEBACDBNFAF-UHFFFAOYSA-M sodium;hexadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCC([O-])=O GGXKEBACDBNFAF-UHFFFAOYSA-M 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- SFZCNBIFKDRMGX-UHFFFAOYSA-N sulfur hexafluoride Chemical compound FS(F)(F)(F)(F)F SFZCNBIFKDRMGX-UHFFFAOYSA-N 0.000 description 1
- 229960000909 sulfur hexafluoride Drugs 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 229960003853 ultrasound contrast media Drugs 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000012800 visualization Methods 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
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
- A61K49/1824—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 coated or functionalised nanoparticles
- A61K49/1827—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 coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle
- A61K49/1851—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 coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule
- A61K49/1857—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 coated or functionalised nanoparticles having a (super)(para)magnetic core, being a solid MRI-active material, e.g. magnetite, or composed of a plurality of MRI-active, organic agents, e.g. Gd-chelates, or nuclei, e.g. Eu3+, encapsulated or entrapped in the core of the coated or functionalised nanoparticle having a (super)(para)magnetic core coated or functionalised with an organic macromolecular compound, i.e. oligomeric, polymeric, dendrimeric organic molecule the organic macromolecular compound being obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. PLGA
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Nanotechnology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Radiology & Medical Imaging (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Acoustics & Sound (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- Immunology (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Biological Depolymerization Polymers (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicinal Preparation (AREA)
- Polyesters Or Polycarbonates (AREA)
- Polyamides (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB929204918A GB9204918D0 (en) | 1992-03-06 | 1992-03-06 | Chemical compounds |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| LTIP391A LTIP391A (en) | 1994-09-25 |
| LT3216B true LT3216B (en) | 1995-04-25 |
Family
ID=10711636
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LTIP391A LT3216B (en) | 1992-03-06 | 1993-03-05 | Contrast agent |
| LTIP388A LT3199B (en) | 1992-03-06 | 1993-03-05 | Biodegradable non-crosslinked polymers of low or zero-water-solubility |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| LTIP388A LT3199B (en) | 1992-03-06 | 1993-03-05 | Biodegradable non-crosslinked polymers of low or zero-water-solubility |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US5574097A (ro) |
| EP (1) | EP0629214B1 (ro) |
| JP (1) | JP3281381B2 (ro) |
| CN (1) | CN1038940C (ro) |
| AT (1) | ATE144540T1 (ro) |
| AU (1) | AU670069B2 (ro) |
| BG (1) | BG99070A (ro) |
| BR (1) | BR9306043A (ro) |
| CA (1) | CA2130671A1 (ro) |
| CZ (1) | CZ281738B6 (ro) |
| DE (1) | DE69305628T2 (ro) |
| DK (1) | DK0629214T3 (ro) |
| ES (1) | ES2093413T3 (ro) |
| FI (1) | FI944078A (ro) |
| GB (1) | GB9204918D0 (ro) |
| GR (1) | GR3022075T3 (ro) |
| HU (1) | HUT69070A (ro) |
| IL (1) | IL104962A (ro) |
| LT (2) | LT3216B (ro) |
| LV (1) | LV10294B (ro) |
| MD (2) | MD940199A (ro) |
| NO (1) | NO303123B1 (ro) |
| NZ (1) | NZ249547A (ro) |
| OA (1) | OA10097A (ro) |
| PH (1) | PH30746A (ro) |
| PL (1) | PL174125B1 (ro) |
| RU (1) | RU2114865C1 (ro) |
| SK (1) | SK105694A3 (ro) |
| WO (1) | WO1993018070A1 (ro) |
| ZA (2) | ZA931594B (ro) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9318288D0 (en) * | 1993-09-03 | 1993-10-20 | 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 |
| CA2164237A1 (en) * | 1994-12-08 | 1996-06-09 | Takeharu Tabuchi | Acrylic monomer |
| US6309999B1 (en) * | 1999-03-19 | 2001-10-30 | Chandra P. Sharma | Process for the preparation of an immunoadsorbent matrix |
| US6720445B2 (en) | 2000-12-21 | 2004-04-13 | Beacon Laboratories, Inc. | Acetyloxymethyl esters and methods for using the same |
| ES2296956T5 (es) | 2001-06-11 | 2011-07-12 | Xenoport, Inc. | Profármacos de análogos de gaba, composiciones y sus usos. |
| US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US6818787B2 (en) | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US7186855B2 (en) | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| AUPR951501A0 (en) * | 2001-12-14 | 2002-01-24 | Smart Drug Systems Inc | Modified sustained release pharmaceutical system |
| NZ536308A (en) | 2002-05-24 | 2009-01-31 | Angiotech Int Ag | Compositions and methods for coating medical implants |
| US8313760B2 (en) | 2002-05-24 | 2012-11-20 | Angiotech International Ag | Compositions and methods for coating medical implants |
| US20030235610A1 (en) * | 2002-06-21 | 2003-12-25 | Piedmont Pharmaceuticals, Llc | Liposomes containing biologically active compounds |
| AU2004293463A1 (en) * | 2003-11-20 | 2005-06-09 | Angiotech International Ag | Implantable sensors and implantable pumps and anti-scarring agents |
| US8795725B2 (en) | 2004-11-04 | 2014-08-05 | Xenoport, Inc. | GABA analog prodrug sustained release oral dosage forms |
| AU2005100176A4 (en) * | 2005-03-01 | 2005-04-07 | Gym Tv Pty Ltd | Garbage bin clip |
| JP2011505179A (ja) | 2007-11-23 | 2011-02-24 | テヒニーシェ ウニヴェルジテート ウィーン | ポリビニルアルコールベースの生分解性、生体適合性、架橋ポリマーの調製用重合硬化性組成物 |
| KR101477935B1 (ko) * | 2010-06-17 | 2014-12-30 | 바스프 에스이 | 사카라이드 측기를 포함하는 중합체 및 그의 용도 |
| RU2543895C2 (ru) * | 2013-05-17 | 2015-03-10 | Общество С Ограниченной Ответственностью "Научно-Производственный Центр "Амфион" | Гидрогелевый материал на основе сшиваемого поливинилового спирта |
| 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 |
| GB201810788D0 (en) * | 2018-06-29 | 2018-08-15 | Biocompatibles Uk Ltd | Biodegradable polymer |
| RU2687231C1 (ru) * | 2018-08-03 | 2019-05-08 | Сергей Борисович Врублевский | Способ получения пигментов |
| CN109928879A (zh) * | 2019-03-05 | 2019-06-25 | 贵州大学 | 一种丙烯酸酯碳酸酯及其均聚物和共聚物材料 |
| CN111892707B (zh) * | 2020-06-18 | 2021-08-13 | 中山大学 | 一种阳离子聚酰胺材料及其制备方法和应用 |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1980002365A1 (en) | 1979-05-04 | 1980-11-13 | Rasor Ass Inc | Ultrasonic image enhancement |
| EP0130935A1 (fr) | 1983-07-01 | 1985-01-09 | Battelle Memorial Institute | Polypeptide biodégradable et son utilisation pour le relargage progressif de médicaments |
| US4774958A (en) | 1985-12-05 | 1988-10-04 | Feinstein Steven B | Ultrasonic imaging agent and method of preparation |
| EP0327490A1 (de) | 1988-02-05 | 1989-08-09 | Schering Aktiengesellschaft | Ultraschallkontrastmittel, Verfahren zu deren Herstellung und deren Verwendung als Diagnostika und Therapeutika |
| WO1991012823A1 (en) | 1990-02-20 | 1991-09-05 | Delta Biotechnology Limited | Diagnostic aid |
| EP0458745A1 (en) | 1990-05-18 | 1991-11-27 | BRACCO International B.V. | Polymeric gas or air filled microballoons usable as suspensions in liquid carriers for ultrasonic echography |
| EP0458079A2 (de) | 1990-04-26 | 1991-11-27 | Hoechst Aktiengesellschaft | Ultraschall-Kontrastmittel, Verfahren zu ihrer Herstellung und Verwendung derselben als Diagnostika und Therapeutika |
| WO1992004392A1 (en) | 1990-09-07 | 1992-03-19 | Holmes, Michael, John | Polymers containing diester units |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4180646A (en) | 1975-01-28 | 1979-12-25 | Alza Corporation | Novel orthoester polymers and orthocarbonate polymers |
| US4356166A (en) * | 1978-12-08 | 1982-10-26 | University Of Utah | Time-release chemical delivery system |
| US4741956A (en) * | 1986-07-09 | 1988-05-03 | Exxon Research And Engineering Company | Biodegradable coatings of ionomer polymer |
-
1992
- 1992-03-06 GB GB929204918A patent/GB9204918D0/en active Pending
-
1993
- 1993-03-05 AU AU36423/93A patent/AU670069B2/en not_active Ceased
- 1993-03-05 DK DK93905526.5T patent/DK0629214T3/da active
- 1993-03-05 ZA ZA931594A patent/ZA931594B/xx unknown
- 1993-03-05 LT LTIP391A patent/LT3216B/lt not_active IP Right Cessation
- 1993-03-05 CZ CZ942152A patent/CZ281738B6/cs unknown
- 1993-03-05 SK SK1056-94A patent/SK105694A3/sk unknown
- 1993-03-05 PL PL93305024A patent/PL174125B1/pl unknown
- 1993-03-05 LT LTIP388A patent/LT3199B/lt not_active IP Right Cessation
- 1993-03-05 DE DE69305628T patent/DE69305628T2/de not_active Expired - Fee Related
- 1993-03-05 JP JP51546393A patent/JP3281381B2/ja not_active Expired - Fee Related
- 1993-03-05 BR BR9306043A patent/BR9306043A/pt not_active Application Discontinuation
- 1993-03-05 ZA ZA931599A patent/ZA931599B/xx unknown
- 1993-03-05 AT AT93905526T patent/ATE144540T1/de not_active IP Right Cessation
- 1993-03-05 ES ES93905526T patent/ES2093413T3/es not_active Expired - Lifetime
- 1993-03-05 WO PCT/GB1993/000469 patent/WO1993018070A1/en active IP Right Grant
- 1993-03-05 NZ NZ249547A patent/NZ249547A/en unknown
- 1993-03-05 CN CN93104053A patent/CN1038940C/zh not_active Expired - Fee Related
- 1993-03-05 US US08/290,875 patent/US5574097A/en not_active Expired - Fee Related
- 1993-03-05 CA CA002130671A patent/CA2130671A1/en not_active Abandoned
- 1993-03-05 IL IL10496293A patent/IL104962A/en not_active IP Right Cessation
- 1993-03-05 EP EP93905526A patent/EP0629214B1/en not_active Expired - Lifetime
- 1993-03-05 LV LVP-93-170A patent/LV10294B/en unknown
- 1993-03-05 HU HU9402563A patent/HUT69070A/hu unknown
- 1993-03-05 RU RU94045151A patent/RU2114865C1/ru active
- 1993-03-08 PH PH45821A patent/PH30746A/en unknown
-
1994
- 1994-07-11 MD MD94-0199A patent/MD940199A/ro unknown
- 1994-07-14 MD MD94-0206A patent/MD940206A/ro unknown
- 1994-08-24 OA OA60557A patent/OA10097A/en unknown
- 1994-09-05 FI FI944078A patent/FI944078A/fi unknown
- 1994-09-05 NO NO943273A patent/NO303123B1/no not_active IP Right Cessation
- 1994-09-28 BG BG99070A patent/BG99070A/bg unknown
-
1996
- 1996-12-18 GR GR960403520T patent/GR3022075T3/el unknown
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1980002365A1 (en) | 1979-05-04 | 1980-11-13 | Rasor Ass Inc | Ultrasonic image enhancement |
| EP0130935A1 (fr) | 1983-07-01 | 1985-01-09 | Battelle Memorial Institute | Polypeptide biodégradable et son utilisation pour le relargage progressif de médicaments |
| US4774958A (en) | 1985-12-05 | 1988-10-04 | Feinstein Steven B | Ultrasonic imaging agent and method of preparation |
| EP0327490A1 (de) | 1988-02-05 | 1989-08-09 | Schering Aktiengesellschaft | Ultraschallkontrastmittel, Verfahren zu deren Herstellung und deren Verwendung als Diagnostika und Therapeutika |
| WO1991012823A1 (en) | 1990-02-20 | 1991-09-05 | Delta Biotechnology Limited | Diagnostic aid |
| EP0458079A2 (de) | 1990-04-26 | 1991-11-27 | Hoechst Aktiengesellschaft | Ultraschall-Kontrastmittel, Verfahren zu ihrer Herstellung und Verwendung derselben als Diagnostika und Therapeutika |
| EP0458745A1 (en) | 1990-05-18 | 1991-11-27 | BRACCO International B.V. | Polymeric gas or air filled microballoons usable as suspensions in liquid carriers for ultrasonic echography |
| WO1992004392A1 (en) | 1990-09-07 | 1992-03-19 | Holmes, Michael, John | Polymers containing diester units |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5795562A (en) | Contrast agents comprising gas-containing or gas-generating microparticles or microballoons | |
| US5674468A (en) | Contrast agents comprising gas-containing or gas-generating polymer microparticles or microballoons | |
| LT3216B (en) | Contrast agent | |
| JP3552721B2 (ja) | ポリマー界面活性剤でカプセル封入された微小気泡および超音波画像形成でのその使用 | |
| US5569449A (en) | Gaseous microparticles as ultrasound contrast agents | |
| JP2003503522A (ja) | 分解性架橋剤およびこれを用いて形成される架橋網目構造ポリマー | |
| JPH06507884A (ja) | 造影剤におけるまたは造影剤に関する改良 | |
| AU701907B2 (en) | Improvements in or relating to contrast agents | |
| KR101127895B1 (ko) | 기체 생성과 생성된 기체의 함유가 가능한 다공성 고분자 마이크로 또는 나노 입자, 이의 제조 방법 및 용도 | |
| EP0686046A1 (en) | Contrast agents | |
| AU665198C (en) | Improvements in or relating to contrast agents |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| TK9A | Rectifications: patents |
Free format text: NYCOMED IMAGING AS, NYCOVEIEN 2, P.O. BOX 4220 TORSHOV, N-0401 OSLO 4, NO, 19951130 |
|
| MM9A | Lapsed patents |
Effective date: 20000305 |