JP2000510108A - 新規な分散性脂質配合物及びそれらの使用 - Google Patents
新規な分散性脂質配合物及びそれらの使用Info
- Publication number
- JP2000510108A JP2000510108A JP09538909A JP53890997A JP2000510108A JP 2000510108 A JP2000510108 A JP 2000510108A JP 09538909 A JP09538909 A JP 09538909A JP 53890997 A JP53890997 A JP 53890997A JP 2000510108 A JP2000510108 A JP 2000510108A
- Authority
- JP
- Japan
- Prior art keywords
- lipid
- mol
- gas
- dipalmitoyl
- microsphere
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 150000002632 lipids Chemical class 0.000 title claims abstract description 255
- 239000000203 mixture Substances 0.000 title claims abstract description 194
- 238000009472 formulation Methods 0.000 title claims description 45
- 239000004005 microsphere Substances 0.000 claims abstract description 179
- 238000000034 method Methods 0.000 claims abstract description 102
- 239000007789 gas Substances 0.000 claims description 171
- 239000007864 aqueous solution Substances 0.000 claims description 80
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 78
- 229920001223 polyethylene glycol Polymers 0.000 claims description 52
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 50
- 239000002202 Polyethylene glycol Substances 0.000 claims description 49
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 46
- 229910052731 fluorine Inorganic materials 0.000 claims description 46
- 239000011737 fluorine Substances 0.000 claims description 46
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 claims description 43
- TXEYQDLBPFQVAA-UHFFFAOYSA-N tetrafluoromethane Chemical compound FC(F)(F)F TXEYQDLBPFQVAA-UHFFFAOYSA-N 0.000 claims description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 38
- 239000000243 solution Substances 0.000 claims description 37
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 28
- 238000004519 manufacturing process Methods 0.000 claims description 22
- 239000002502 liposome Substances 0.000 claims description 20
- 239000003937 drug carrier Substances 0.000 claims description 18
- 238000004108 freeze drying Methods 0.000 claims description 18
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 claims description 18
- 229960004065 perflutren Drugs 0.000 claims description 18
- 238000001914 filtration Methods 0.000 claims description 17
- KAVGMUDTWQVPDF-UHFFFAOYSA-N perflubutane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)F KAVGMUDTWQVPDF-UHFFFAOYSA-N 0.000 claims description 16
- 229950003332 perflubutane Drugs 0.000 claims description 16
- 238000011049 filling Methods 0.000 claims description 14
- 239000002245 particle Substances 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 13
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- 229910018503 SF6 Inorganic materials 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 229960004624 perflexane Drugs 0.000 claims description 12
- ZJIJAJXFLBMLCK-UHFFFAOYSA-N perfluorohexane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F ZJIJAJXFLBMLCK-UHFFFAOYSA-N 0.000 claims description 12
- 239000011148 porous material Substances 0.000 claims description 12
- SFZCNBIFKDRMGX-UHFFFAOYSA-N sulfur hexafluoride Chemical compound FS(F)(F)(F)(F)F SFZCNBIFKDRMGX-UHFFFAOYSA-N 0.000 claims description 12
- 229960000909 sulfur hexafluoride Drugs 0.000 claims description 12
- 238000010438 heat treatment Methods 0.000 claims description 10
- 239000002356 single layer Substances 0.000 claims description 10
- 239000004698 Polyethylene Substances 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 229920000573 polyethylene Polymers 0.000 claims description 8
- 230000007704 transition Effects 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- 239000004973 liquid crystal related substance Substances 0.000 claims description 7
- UYHAERNXVVKSCT-PGUFJCEWSA-N 1,2-dipalmitoyl-sn-glycero-3-phosphoethanol Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCC)OC(=O)CCCCCCCCCCCCCCC UYHAERNXVVKSCT-PGUFJCEWSA-N 0.000 claims description 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 6
- 238000003260 vortexing Methods 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- 239000002504 physiological saline solution Substances 0.000 claims description 4
- SLKDGVPOSSLUAI-PGUFJCEWSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine zwitterion Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OCCN)OC(=O)CCCCCCCCCCCCCCC SLKDGVPOSSLUAI-PGUFJCEWSA-N 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 2
- 229960004692 perflenapent Drugs 0.000 claims 7
- NJCBUSHGCBERSK-UHFFFAOYSA-N perfluoropentane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F NJCBUSHGCBERSK-UHFFFAOYSA-N 0.000 claims 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 1
- 235000014113 dietary fatty acids Nutrition 0.000 claims 1
- 229930195729 fatty acid Natural products 0.000 claims 1
- 239000000194 fatty acid Substances 0.000 claims 1
- 150000004665 fatty acids Chemical class 0.000 claims 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 claims 1
- 238000012377 drug delivery Methods 0.000 abstract description 2
- 238000012285 ultrasound imaging Methods 0.000 abstract description 2
- 229940126585 therapeutic drug Drugs 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000010410 layer Substances 0.000 description 16
- 239000008365 aqueous carrier Substances 0.000 description 15
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
- 239000006185 dispersion Substances 0.000 description 14
- 238000004128 high performance liquid chromatography Methods 0.000 description 12
- 238000004513 sizing Methods 0.000 description 12
- 239000012071 phase Substances 0.000 description 11
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
- 239000013011 aqueous formulation Substances 0.000 description 10
- 238000001035 drying Methods 0.000 description 10
- -1 lipid dipalmitoyl phosphate Chemical class 0.000 description 10
- 238000007710 freezing Methods 0.000 description 9
- 230000008014 freezing Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 8
- 238000003384 imaging method Methods 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- 238000001125 extrusion Methods 0.000 description 7
- 230000033001 locomotion Effects 0.000 description 6
- 239000011159 matrix material Substances 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 239000002872 contrast media Substances 0.000 description 5
- 238000009826 distribution Methods 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000001954 sterilising effect Effects 0.000 description 5
- 238000004659 sterilization and disinfection Methods 0.000 description 5
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 230000018044 dehydration Effects 0.000 description 4
- 238000006297 dehydration reaction Methods 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 230000000087 stabilizing effect Effects 0.000 description 4
- 239000008223 sterile water Substances 0.000 description 4
- 241000183024 Populus tremula Species 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 239000003570 air Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000002059 diagnostic imaging Methods 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- 238000005516 engineering process Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000007935 neutral effect Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- QJQZRLXDLORINA-UHFFFAOYSA-N 2-cyclohexylethanol Chemical compound OCCC1CCCCC1 QJQZRLXDLORINA-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 101000957776 Escherichia coli O157:H7 Mannose-1-phosphate guanylyltransferase 1 Proteins 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 229910000831 Steel Inorganic materials 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 235000011089 carbon dioxide Nutrition 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical group C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000010408 film Substances 0.000 description 2
- 238000011194 good manufacturing practice Methods 0.000 description 2
- 238000000265 homogenisation Methods 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 125000001312 palmitoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- BBEAQIROQSPTKN-UHFFFAOYSA-N pyrene Chemical compound C1=CC=C2C=CC3=CC=CC4=CC=C1C2=C43 BBEAQIROQSPTKN-UHFFFAOYSA-N 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000000527 sonication Methods 0.000 description 2
- 239000010959 steel Substances 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 239000010409 thin film Substances 0.000 description 2
- 238000002604 ultrasonography Methods 0.000 description 2
- 238000009827 uniform distribution Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- QFMZQPDHXULLKC-UHFFFAOYSA-N 1,2-bis(diphenylphosphino)ethane Chemical group C=1C=CC=CC=1P(C=1C=CC=CC=1)CCP(C=1C=CC=CC=1)C1=CC=CC=C1 QFMZQPDHXULLKC-UHFFFAOYSA-N 0.000 description 1
- JRHNUZCXXOTJCA-UHFFFAOYSA-N 1-fluoropropane Chemical compound CCCF JRHNUZCXXOTJCA-UHFFFAOYSA-N 0.000 description 1
- 101000957777 Escherichia coli O157:H7 Mannose-1-phosphate guanylyltransferase 2 Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 239000000232 Lipid Bilayer Substances 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 101100059320 Mus musculus Ccdc85b gene Proteins 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 239000004721 Polyphenylene oxide Substances 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 239000012080 ambient air Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000012867 bioactive agent Substances 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940039231 contrast media Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 150000002016 disaccharides Chemical class 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000002961 echo contrast media Substances 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 239000010419 fine particle Substances 0.000 description 1
- GVEPBJHOBDJJJI-UHFFFAOYSA-N fluoranthrene Natural products C1=CC(C2=CC=CC=C22)=C3C2=CC=CC3=C1 GVEPBJHOBDJJJI-UHFFFAOYSA-N 0.000 description 1
- 210000000245 forearm Anatomy 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- SUHOQUVVVLNYQR-MRVPVSSYSA-O glycerylphosphorylcholine Chemical compound C[N+](C)(C)CCO[P@](O)(=O)OC[C@H](O)CO SUHOQUVVVLNYQR-MRVPVSSYSA-O 0.000 description 1
- 239000004519 grease Substances 0.000 description 1
- UKACHOXRXFQJFN-UHFFFAOYSA-N heptafluoropropane Chemical compound FC(F)C(F)(F)C(F)(F)F UKACHOXRXFQJFN-UHFFFAOYSA-N 0.000 description 1
- WMIYKQLTONQJES-UHFFFAOYSA-N hexafluoroethane Chemical compound FC(F)(F)C(F)(F)F WMIYKQLTONQJES-UHFFFAOYSA-N 0.000 description 1
- 239000012052 hydrophilic carrier Substances 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000012538 light obscuration Methods 0.000 description 1
- 125000003473 lipid group Chemical group 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000012792 lyophilization process Methods 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000004530 micro-emulsion Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 239000002353 niosome Substances 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- BCCOBQSFUDVTJQ-UHFFFAOYSA-N octafluorocyclobutane Chemical compound FC1(F)C(F)(F)C(F)(F)C1(F)F BCCOBQSFUDVTJQ-UHFFFAOYSA-N 0.000 description 1
- 235000019407 octafluorocyclobutane Nutrition 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- 150000008103 phosphatidic acids Chemical class 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920000570 polyether Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- ALDITMKAAPLVJK-UHFFFAOYSA-N prop-1-ene;hydrate Chemical group O.CC=C ALDITMKAAPLVJK-UHFFFAOYSA-N 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000003756 stirring Methods 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
- 238000010257 thawing Methods 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000402 unacceptable toxicity Toxicity 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0028—Disruption, e.g. by heat or ultrasounds, sonophysical or sonochemical activation, e.g. thermosensitive or heat-sensitive liposomes, disruption of calculi with a medicinal preparation and ultrasounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0052—Thermotherapy; Hyperthermia; Magnetic induction; Induction heating therapy
-
- 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
-
- 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
-
- 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
- A61K49/227—Liposomes, lipoprotein vesicles, e.g. LDL or HDL lipoproteins, micelles, e.g. phospholipidic or polymeric
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
- A61K9/1277—Processes for preparing; Proliposomes
- A61K9/1278—Post-loading, e.g. by ion or pH gradient
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
- G01R33/54—Signal processing systems, e.g. using pulse sequences ; Generation or control of pulse sequences; Operator console
- G01R33/56—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution
- G01R33/5601—Image enhancement or correction, e.g. subtraction or averaging techniques, e.g. improvement of signal-to-noise ratio and resolution involving use of a contrast agent for contrast manipulation, e.g. a paramagnetic, super-paramagnetic, ferromagnetic or hyperpolarised contrast agent
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
- A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
- A61M5/178—Syringes
- A61M5/31—Details
- A61M5/3145—Filters incorporated in syringes
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Pharmacology & Pharmacy (AREA)
- Radiology & Medical Imaging (AREA)
- Dispersion Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Acoustics & Sound (AREA)
- Engineering & Computer Science (AREA)
- Signal Processing (AREA)
- High Energy & Nuclear Physics (AREA)
- Condensed Matter Physics & Semiconductors (AREA)
- General Physics & Mathematics (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Abstract
Description
Claims (1)
- 【特許請求の範囲】 1. 水性の製薬学的に許容しうる担休中に分散された、それぞれ約70ない し約90モル%、約5ないし約15モル%及び約5ないし約15モル%の比率の 凍結乾燥組成物脂質ジパルミトイルホスファチジルコリン、ジパルミトイルホス ファチジルエタノールアミン−ポリエチレングリコール及びジパルミトイルホス ファチジン酸の再構成された配合物を含んでなる気体充填微小球であって、製薬 学的に許容しうる担体中の脂質の合計濃度が約0.1mg/mlないし約5mg /mlであり、気体充填微小球中の該気体がフッ素含有気体である気体充填微小 球。 2. それぞれ約80ないし約85モル%、約5ないし約10モル%及び約5 ないし約10モル%の比率のジパルミトィルホスファチジルコリン、ジパルミト イルホスファチジルエタノールアミン−ポリエチレングリコール及びジパルミト イルホスファチジン酸を含んでなる請求の範囲第1項の気体充填微小球。 3. それぞれ約82モル%、約8モル%及び約10モル%の比率のジパルミ トイルホスファチジルコリン、ジパルミトイルホスファチジルエタノールアミン −ポリエチレングリコール及びジパルミトイルホスファチジン酸を含んでなる請 求の範囲第1項の気体充填微小球。 4. 該フッ素含有気体が六フッ化硫黄及びペルフルオロカーボンからなる群 から選択される請求の範囲第1項の気体充填微小球。 5. 該ペルフルオロカーボンがペルフルオロプロパン、ペルフルオロペンタ ン、ペルフルオロヘキサン及びペルフルオロブタンからなる群から選択される請 求の範囲第4項の気体充填微小球。 6. 脂質の総合濃度が製薬学的に許容しうる担体で約1mg/ml である請求の範囲第1項の気体充填微小球。 7. 製薬学的に許容しうる担体がそれぞれ8:1:1、v:v:vの比率の 水、グリセロール及びプロピレングリコールの混合物並びに食塩水、グリセロー ル及びプロピレングリコールの混合物からなる群から選択される請求の範囲第1 項の気体充填微小球。 8. ポリエチレングリコールが約400ないし約200,000の間の分子 量である請求の範囲第1項の気体充填微小球。 9. ポリエチレングリコールが約1,000ないし約20,000の間の分 子量である請求の範囲第1項の気体充填微小球。 10. ポリエチレングリコールが約2,000ないし約8,000の間の分 子量である請求の範囲第1項の気体充填微小球。 11. ポリエチレングリコールが約5,000の分子量である請求の範囲第 1項の気体充填微小球。 12. 水溶液中約20mg/mlないし約50mg/mlの総合濃度の脂質 を凍結乾燥することにより製造された、脂質ジパルミトイルホスファチジルコリ ン、ジパルミトイルホスファチジルエタノールアミン−ポリエチレングリコール 及びジパルミトイルホスファチジン酸をそれぞれ水溶液中に約70ないし約90 モル%、約5ないし約15モル%及び約5ないし約15モル%の比率で含んでな る凍結乾燥脂質組成物。 13. それぞれ約80ないし約85モル%、約5ないし約10モル%及び約 5ないし約10モル%の比率のジパルミトイルホスファチジルコリン、ジパルミ トイルホスファチジルエタノールアミン−ポリエチレングリコール及びジパルミ トイルホスファチジン酸を含んでなる請求の範囲第12項の脂質組成物。 14. それぞれ約82モル%、約8モル%及び約10モル%の比率のジパル ミトイルホスファチジルコリン、ジパルミトイルホスファチジルエタノールアミ ン−ポリエチレングリコール及びジパルミトイルホスファチジン酸を含んでなる 請求の範囲第12項の脂質組成物。 15. それぞれ約82モル%、約8モル%及び約10モル%の比率のジパル ミトイルホスファチジルコリン、ジパルミトイルホスファチジルエタノールアミ ン−ポリエチレングリコール及びジパルミトイルホスファチジン酸を含んでなり 、脂質の総合濃度が凍結乾燥前の水溶液で約25mg/mlである請求の範囲第 12項の脂質組成物。 16. 該組成物が綿状である請求の範囲第12項の脂質組成物。 17. 該水溶液が水、バッファー、生理的食塩水及び等張食塩水からなる群 から選択される請求の範囲第12項の脂質組成物。 18. ポリエチレングリコールが約400ないし約200,000の間の分 子量である請求の範囲第12項の脂質組成物。 19. ポリエチレングリコールが約1,000ないし約20,000の間の 分子量である請求の範囲第12項の脂質組成物。 20. ポリエチレングリコールが約2,000ないし約8,000の間の分 子量である請求の範囲第12項の脂質組成物。 21. ポリエチレングリコールが約5,000の分子量である請求の範囲第 12項の脂質組成物。 22. a.脂質ジパルミトイルホスファチジルコリン、ジパルミトイルホス ファチジルエタノールアミン−ポリエチレングリコール及びジパルミトイルホス ファチジン酸をそれぞれ約70ないし約90モル%、約5ないし約15モル%及 び約5ないし約15モル%の比率で含んでな り、脂質の総合濃度が凍結乾燥前の水溶液で約20mg/mlないし約50mg /mlである凍結乾燥脂質組成物を得; b.該凍結乾燥組成物を水性の製薬学的に許容しうる担体中に約0. 1mg/mlないし約5mg/mlの濃度に分散させて微小球形成水溶液を生ぜ しめ; c.該微小球形成溶液中にフッ素含有気体を入れ;そして d.該微小球形成水溶液を振盪してフッ素含有気体が充填された微小 球を形成する ことを含んでなる気体充填微小球の製造方法。 23. 振盪工程がボルテックスすることを含んでなる請求の範囲第22項の 方法。 24. 該微小球形成水溶液を濾過する工程をさらに含んでなる請求の範囲第 22項の方法。 25. 選択される孔径の少なくとも1枚のフィルターを通して該微小球形成 水溶液を押し出すことをさらに含んでなる請求の範囲第22項の方法。 26. 孔径が約10μmまたはそれより小さい請求の範囲第25項の方法。 27. 孔径が約0.22μmである請求の範囲第25項の方法。 28. 該微小球形成水溶液を加熱することをさらに含んでなる請求の範囲第 22項の方法。 29. 該微小球形成水溶液を少なくとも1個の容器中に分散させることをさ らに含んでなる請求の範囲第25項の方法。 30. 工程cが該微小球形成水溶液を含有する容器を室中に置き、 該室中にフッ素含有気体を入れることを含んでなり、そして工程dが該容器を振 盪してフッ素含有気体が充填された微小球を形成することを含んでなる請求の範 囲第22項の方法。 31. 該容器を加圧することをさらに含んでなる請求の範囲第30項の方法 。 32. 工程cが該微小球形成水溶液を含有する容器を加圧された室中に置き 、室から気体を吸い出し、容器の充填空積がフッ素含有気体で満たされるように 室にフッ素含有気体を入れることを含んでなり、そして工程dが該容器を振盪し てフッ素含有気体が充填された微小球を形成することを含んでなる請求の範囲第 22項の方法。 33. 該水溶液が水、生理的食塩水及び等張食塩水よりなる群から選択され る請求の範囲第22項の方法。 34. 該製薬学的に許容しうる担体がそれぞれ8:1:1、v:v:vの比 率の、水、グリセロール及びプロピレングリコールの混合物並びに食塩水、グリ セロール及びプロピレングリコールの混合物よりなる群から選択される請求の範 囲第22項の方法。 35. 該フッ素含有気体が六フッ化硫黄及びペルフルオロカーボンよりなる 群から選択される請求の範囲第22項の方法。 36. 該ペルフルオロカーボンがペルフルオロプロパン、ペルフルオロペン タン、ペルフルオロヘキサン及びペルフルオロブタンからなる群から選択される 請求の範囲第35項の方法。 37. a.それぞれ約70ないし約90モル%、約5ないし約15モル%及 び約5ないし約15モル%の比率の脂質ジパルミトイルホスファチジルコリン、 ジパルミトイルホスファチジルエタノールアミン−ポリ エチレングリコール及びジパルミトイルホスファチジン酸を水溶液中に約20m g/mlないし約50mg/mlの濃度に再構成して脂質含有水溶液を生ぜしめ ; b.該脂質含有水溶液を凍結乾燥してそれぞれ約70ないし約90モ ル%、約5ないし約15モル%及び約5ないし約15モル%のジパルミトイルス ファチジルコリン、ジパルミトイルホスファチジルエタノールアミン−ポリエチ レングリコール及びジパルミトイルホスファチジン酸比率が組成物の全体にわた って均一であるような凍結乾燥組成物を生ぜしめ; c.該凍結乾燥組成物を水性の製薬学的に許容しうる担体中に約0. 1mg/mlないし約5mg/mlの濃度に分散させて微小球形成水溶液を生ぜ しめ; d.該微小球形成溶液中にフッ素含有気体を入れ;そして e.該微小球形成水溶液を振盪してフッ素含有気体が充填された微小 球を形成する ことを含んでなるフッ素含有気体充填微小球の製造方法。 38. 振盪工程がボルテックスすることを含んでなる請求の範囲第37項の 方法。 39. 該微小球形成水溶液を濾過する工程をさらに含んでなる請求の範囲第 37項の方法。 40. 選択される孔径の少なくとも1枚のフィルターを通して該微小球形成 水溶液を押し出すことをさらに含んでなる請求の範囲第37項の方法。 41. 孔径が約10μmまたはそれより小さい請求の範囲第40項 の方法。 42. 孔径が約0.22μmである請求の範囲第40項の方法。 43. 該微小球形成水溶液を加熱することをさらに含んでなる請求の範囲第 37項の方法。 44. 該微小球形成水溶液を少なくとも1個の容器中に分散させることをさ らに含んでなる請求の範囲第40項の方法。 45. 工程d.が該微小球形成水溶液を含有する容器を室中に置き、該室中 にフッ素含有気体を入れることを含んでなり、そして工程e.が該容器を振盪し てフッ素含有気体が充填された微小球を形成することを含んでなる請求の範囲第 37項の方法。 46. 該容器を加圧することをさらに含んでなる請求の範囲第45項の方法 。 47. 工程d.が該微小球形成水溶液を含有する容器を加圧された室中に置 き、室から気体を吸い出し、容器の充填空積がフッ素含有気体で満たされるよう に室にフッ素含有気体を入れることを含んでなり、そして工程e.が該容器を振 盪してフッ素含有気体が充填された微小球を形成することを含んでなる請求の範 囲第37項の方法。 48. 該水溶液が水、生理的食塩水及び等張食塩水からなる群から選択され る請求の範囲第37項の方法。 49. 該製薬学的に許容しうる担体がそれぞれ8:1:1、v:v:vの比 率の水:グリセロール及びプロピレングリコールの混合物並びに食塩水、グリセ ロール及びプロピレングリコールの混合物よりなる群から選択される請求の範囲 第37項の方法。 50. 工程d.が該微小球形成水溶液を含有する容器を室中に置き、 ペルフルオロカーボンを入れることを含んでなり、そして工程e.が該容器を振 盪してペルフルオロカーボンを含有する微小球を形成することを含んでなる請求 の範囲第37項の方法。 51. 工程d.が該微小球形成水溶液を含有する容器を室中に置き、該室中 にペルフルオロプロパン及びペルフルオロブタンよりなる群から選択されるペル フルオロカーボンを入れることを含んでなり、そして工程e.が該容器を振盪し てペルフルオロカーボンを含有する微小球を形成することを含んでなる請求の範 囲第50項の方法。 52. 工程d.が該微小球形成水溶液を含有する容器を加圧された室中に置 き、室から気体を吸い出し、容器の充填空積がペルフルオロカーボンで満たされ るように室にペルフルオロカーボンを入れることを含んでなり、そして工程e. が該容器を振盪してペルフルオロカーボンを含有する微小球を形成することを含 んでなる請求の範囲第37項の方法。 53. 工程d.が該微小球形成水溶液を含有する容器を加圧された室中に置 き、室から気体を吸い出し、容器の充填空積がペルフルオロカーボンで満たされ るようにペルフルオロプロパン及びペルフルオロブタンよりなる群から選択され るペルフルオロカーボンを室に入れることを含んでなり、そして工程e.が該容 器を振盪してペルフルオロカーボンを含有する微小球を形成することを含んでな る請求の範囲第52項の方法。 54. 該フッ素含有気体が六フッ化硫黄及びペルフルオロカーボンよりなる 群から選択される請求の範囲第37項の方法。 55. 該ペルフルオロカーボンがペルフルオロプロパン、ペルフルオロペン タン、ペルフルオロヘキサン及びペルフルオロブタンよりなる 群から選択される請求の範囲第54項の方法。 56. a.それぞれ約82モル%、約8モル%及び約10モル%の比率の脂 質ジパルミトイルホスファチジルコリン、ジパルミトイルホスファチジルエタノ ールアミン−ポリエチレングリコール及びジパルミトイルホスファチジン酸を約 25mg/mlの濃度に水溶液中に分散させて脂質含有水溶液を生ぜしめ; b.該脂質含有水溶液を凍結乾燥してそれぞれ約82モル%、約8モ ル%及び約10モル%のジパルミトイルホスファチジルコリン、ジパルミトイル ホスファチジルエタノールアミン−ポリエチレングリコール及びジパルミトイル ホスファチジン酸比率が組成物の全体にわたって均一であるような凍結乾燥組成 物を生ぜしめ; c.該凍結乾燥組成物を水性の製薬学的に許容しうる担体中に約1m g/mlの濃度に分散させて微小球形成水溶液を生ぜしめ; d.該微小球形成溶液中を加熱し; e.約0.22μmの孔を有するフィルターを通して該微小球形成水 溶液を濾過し、 f.該微小球形成水溶液を少なくとも1個の容器中に分散させ、容器 を加圧された室中に置き、そして該室を真空にし; g.容器の充填空積がフッ素含有気体で満たされるように該室中にフ ッ素含有気体を入れ;そして h.該容器を振盪してフッ素含有気体が充填された微小球を形成する ことを含んでなる気体充填微小球の製造方法。 57. 工程h.が脂質のゲルから液晶への相転移温度より低い温度 で実施される請求の範囲第56項の方法。 58. 該フッ素含有気体が六フッ化硫黄及びペルフルオロカーボンよりなる 群から選択される請求の範囲第56項の方法。 59. 該ペルフルオロカーボンがペルフルオロプロパン、ペルフルオロペン タン、ペルフルオロヘキサン及びペルフルオロブタンよりなる群から選択される 請求の範囲第58項の方法。 60. a.それぞれ約70ないし約90モル%、約5ないし約15モル%及 び約5ないし約15モル%の比率の脂質ジパルミトイルホスファチジルコリン、 ジパルミトイルホスファチジルエタノールアミン−ポリエチレングリコール及び ジパルミトイルホスファチジン酸を約20ないし約50mg/mlの濃度に水溶 液中に分散させて脂質含有水溶液を生ぜしめ;そして b.該脂質含有水溶液を凍結乾燥してそれぞれ約70ないし90モル %、約5ないし約15モル%及び約5ないし約15モル%のジパルミトイルホス ファチジルコリン、ジパルミトイルホスファチジルエタノールアミン−ポリエチ レングリコール及びジパルミトイルホスファチジン酸比率が組成物の全体にわた って均一であるような凍結乾燥組成物を生ぜしめる ことを含んでなる凍結乾燥脂質組成物の製造方法。 61. 該組成物が綿状である請求の範囲第60項の方法。 62. 該水溶液が水、生理的食塩水及び等張食塩水よりなる群から選択され る請求の範囲第60項の方法。 63. a.それぞれ約80ないし約85モル%、約5ないし約10モル%及 び約5ないし約10モル%の比率の脂質ジパルミトイルホスファ チジルコリン、ジパルミトイルホスファチジルエタノールアミン−ポリエチレン グリコール及びジパルミトイルホスファチジン酸を約20ないし約50mg/m lの濃度に水溶液中に分散させて脂質含有水溶液を生ぜしめ;そして b.該脂質含有水溶液を凍結乾燥してそれぞれ約80ないし85モル %、約5ないし約10モル%及び約5ないし約10モル%のジパルミトイルホス ファチジルコリン、ジパルミトイルホスファチジルエタノールアミン−ポリエチ レングリコール及びジパルミトイルホスファチジン酸比率が組成物の全体にわた って均一であるような凍結乾燥組成物を生ぜしめる ことを含んでなる請求の範囲第60項の方法。 64. a.それぞれ約82モル%、約8モル%及び約10モル%の比率の脂 質ジパルミトイルホスファチジルコリン、ジパルミトイルホスファチジルエタノ ールアミン−ポリエチレングリコール及びジパルミトイルホスファチジン酸を約 20ないし約50mg/mlの濃度に水溶液中に分散させて脂質含有水溶液を生 ぜしめ;そして b.該脂質含有水溶液を凍結乾燥してそれぞれ約82モル%、約8モ ル%及び約10モル%のジパルミトイルホスファチジルコリン、ジパルミトイル ホスファチジルエタノールアミン−ポリエチレングリコール及びジパルミトイル ホスファチジン酸比率が組成物の全体にわたって均一であるような凍結乾燥組成 物を生ぜしめる ことを含んでなる請求の範囲第60項の方法。 65. a.それぞれ約82モル%、約8モル%及び約10モル%の比率の脂 質ジパルミトイルホスファチジルコリン、ジパルミトイルホス ファチジルエタノールアミン−ポリエチレングリコール及びジパルミトイルホス ファチジン酸を約25mg/mlの濃度に水溶液中に分散させて脂質含有水溶液 を生ぜしめ;そして b.該脂質含有水溶液を凍結乾燥してそれぞれ約82モル%、約8モ ル%及び約10モル%のジパルミトイルホスファチジルコリン、ジパルミトイル ホスファチジルエタノールアミン−ポリエチレングリコール及びジパルミトイル ホスファチジン酸比率が組成物の全体にわたって均一であるような凍結乾燥組成 物を生ぜしめる ことを含んでなる請求の範囲第60項の方法。 66. 該脂質が単層を含んでなる請求の範囲第1項の微小球。 67. 該気体が六フッ化硫黄及びペルフルオロカーボンよりなる群から選択 される請求の範囲第66項の微小球。 68. 該ペルフルオロカーボンがペルフルオロブタン、ペルフルオロプロパ ン、ペルフルオロペンタン及びペルフルオロヘキサンよりなる群から選択される 請求の範囲第67項の微小球。 69. 該脂質が単層を含んでなる請求の範囲第12項の凍結乾燥脂質組成物 。 70. 該気体が六フッ化硫黄及びペルフルオロカーボンよりなる群から選択 される請求の範囲第69項の凍結乾燥脂質組成物。 71. 該ペルフルオロカーボンがペルフルオロブタン、ペルフルオロプロパ ン、ペルフルオロペンタン及びペルフルオロヘキサンよりなる群から選択される 請求の範囲第70項の凍結乾燥脂質組成物。 72. 該脂質が単層を含んでなる請求の範囲第22項の方法。 73. 該気体が六フッ化硫黄及びペルフルオロカーボンよりなる群 から選択される請求の範囲72の方法。 74. 該ペルフルオロカーボンがペルフルオロブタン、ペルフルオロプロパ ン、ペルフルオロペンタン及びペルフルオロヘキサンよりなる群から選択される 請求の範囲第73項の方法。 75. 該脂質が単層を含んでなる請求の範囲第37項の方法。 76. 該気体が六フッ化硫黄及びペルフルオロカーボンよりなる群から選択 される請求の範囲第75項の方法。 77. 該ペルフルオロカーボンがペルフルオロブタン、ペルフルオロプロパ ン、ペルフルオロペンタン及びペルフルオロヘキサンよりなる群から選択される 請求の範囲第76項の方法。 78. 該脂質が単層を含んでなる請求の範囲第56項の方法。 79. 該気体が六フッ化硫黄及びペルフルオロカーボンよりなる群から選択 される請求の範囲第78項の方法。 80. 該ペルフルオロカーボンがペルフルオロブタン、ペルフルオロプロパ ン、ペルフルオロペンタン及びペルフルオロヘキサンよりなる群から選択される 請求の範囲第79項の方法。 81. 該脂質が単層を含んでなる請求の範囲第60項の方法。 82. 該気体が六フッ化硫黄及びペルフルオロカーボンよりなる群から選択 される請求の範囲第81項の方法。 83. 該ペルフルオロカーボンがペルフルオロブタン、ペルフルオロプロパ ン、ペルフルオロペンタン及びペルフルオロヘキサンよりなる群から選択される 請求の範囲第82項の方法。 84. 架橋または重合されたリポソームを含んでなる請求の範囲第1項の気 体充填微小球。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US08/643,070 US5776429A (en) | 1989-12-22 | 1996-04-30 | Method of preparing gas-filled microspheres using a lyophilized lipids |
US08/643,070 | 1996-04-30 | ||
PCT/US1997/005908 WO1997040858A1 (en) | 1996-04-30 | 1997-04-02 | Novel dispersible lipid blends and uses therefor |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008146776A Division JP2008260775A (ja) | 1996-04-30 | 2008-06-04 | 新規な分散性脂質配合物及びそれらの使用 |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2000510108A true JP2000510108A (ja) | 2000-08-08 |
JP2000510108A5 JP2000510108A5 (ja) | 2004-12-09 |
Family
ID=24579245
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP09538909A Ceased JP2000510108A (ja) | 1996-04-30 | 1997-04-02 | 新規な分散性脂質配合物及びそれらの使用 |
JP2008146776A Pending JP2008260775A (ja) | 1996-04-30 | 2008-06-04 | 新規な分散性脂質配合物及びそれらの使用 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2008146776A Pending JP2008260775A (ja) | 1996-04-30 | 2008-06-04 | 新規な分散性脂質配合物及びそれらの使用 |
Country Status (6)
Country | Link |
---|---|
US (2) | US5776429A (ja) |
EP (1) | EP0923383A4 (ja) |
JP (2) | JP2000510108A (ja) |
CN (1) | CN1216925A (ja) |
AU (1) | AU2451097A (ja) |
WO (1) | WO1997040858A1 (ja) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008526785A (ja) * | 2005-01-10 | 2008-07-24 | チョンチン・ハイフ(エイチアイエフユー)・テクノロジー・カンパニー・リミテッド | 高密度焦点式超音波療法のための増強剤および同剤のスクリーニングの方法 |
Families Citing this family (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20020150539A1 (en) * | 1989-12-22 | 2002-10-17 | Unger Evan C. | Ultrasound imaging and treatment |
US5776429A (en) * | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US6989141B2 (en) * | 1990-05-18 | 2006-01-24 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US20010024638A1 (en) * | 1992-11-02 | 2001-09-27 | Michel Schneider | Stable microbubble suspensions as enhancement agents for ultrasound echography and dry formulations thereof |
US7083778B2 (en) * | 1991-05-03 | 2006-08-01 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US5578292A (en) | 1991-11-20 | 1996-11-26 | Bracco International B.V. | Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof |
US6613306B1 (en) | 1990-04-02 | 2003-09-02 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
IN172208B (ja) | 1990-04-02 | 1993-05-01 | Sint Sa | |
US20040208826A1 (en) * | 1990-04-02 | 2004-10-21 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
US5445813A (en) * | 1992-11-02 | 1995-08-29 | Bracco International B.V. | Stable microbubble suspensions as enhancement agents for ultrasound echography |
USRE39146E1 (en) | 1990-04-02 | 2006-06-27 | Bracco International B.V. | Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof |
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 |
US20030194376A1 (en) * | 1990-05-18 | 2003-10-16 | Bracco International B.V. | Ultrasound contrast agents and methods of making and using them |
EP0504881B2 (en) * | 1991-03-22 | 2000-11-08 | Katsuro Tachibana | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
IL104084A (en) | 1992-01-24 | 1996-09-12 | Bracco Int Bv | Sustainable aqueous suspensions of pressure-resistant and gas-filled blisters, their preparation, and contrast agents containing them |
US5798091A (en) | 1993-07-30 | 1998-08-25 | Alliance Pharmaceutical Corp. | Stabilized gas emulsion containing phospholipid for ultrasound contrast enhancement |
US7083572B2 (en) * | 1993-11-30 | 2006-08-01 | Bristol-Myers Squibb Medical Imaging, Inc. | Therapeutic delivery systems |
DE69432295T2 (de) * | 1993-12-15 | 2003-08-14 | Bracco Research Sa | Gas-mischungen verwendbar als ultraschallkontrastmittel |
US6645463B1 (en) | 1994-05-16 | 2003-11-11 | The Board Of Regents Of The University Of Michigan | Blood-pool selective carrier for lipophilic imaging agents |
US6521211B1 (en) * | 1995-06-07 | 2003-02-18 | Bristol-Myers Squibb Medical Imaging, Inc. | Methods of imaging and treatment with targeted compositions |
US6033645A (en) * | 1996-06-19 | 2000-03-07 | Unger; Evan C. | Methods for diagnostic imaging by regulating the administration rate of a contrast agent |
EP0973553A2 (en) * | 1997-04-11 | 2000-01-26 | The Board Of Regents Of The University Of Michigan | Blood-pool carrier for lipophilic imaging agents |
US6582392B1 (en) | 1998-05-01 | 2003-06-24 | Ekos Corporation | Ultrasound assembly for use with a catheter |
US6676626B1 (en) | 1998-05-01 | 2004-01-13 | Ekos Corporation | Ultrasound assembly with increased efficacy |
US20050019266A1 (en) * | 1997-05-06 | 2005-01-27 | Unger Evan C. | Novel targeted compositions for diagnostic and therapeutic use |
US6416740B1 (en) * | 1997-05-13 | 2002-07-09 | Bristol-Myers Squibb Medical Imaging, Inc. | Acoustically active drug delivery systems |
AU7702798A (en) * | 1997-05-30 | 1998-12-30 | Alliance Pharmaceutical Corporation | Methods and apparatus for monitoring and quantifying the movement of fluid |
GB9717589D0 (en) * | 1997-08-19 | 1997-10-22 | Nycomed Imaging As | Improvements in or relating to contrast agents |
US6086540A (en) * | 1997-10-07 | 2000-07-11 | Molecular Biosystems, Inc. | Methods of ultrasound imaging using echogenically persistent contrast agents |
US20010003580A1 (en) * | 1998-01-14 | 2001-06-14 | Poh K. Hui | Preparation of a lipid blend and a phospholipid suspension containing the lipid blend |
RU2207808C2 (ru) * | 1998-04-09 | 2003-07-10 | Амершем Хелт АС | Применение контрастных агентов в форме частиц в диагностической визуализации для изучения физиологических параметров |
GB9808599D0 (en) * | 1998-04-22 | 1998-06-24 | Nycomed Imaging As | Improvements in or realting to contrast agents |
GB9809084D0 (en) * | 1998-04-28 | 1998-06-24 | Nycomed Imaging As | Improvements in or relating to diagnostic/therapeutic agents |
US6548048B1 (en) | 1998-04-28 | 2003-04-15 | Amersham Health As | Lipopeptide stabilized microbubbles as diagnostic/therapeutic agents |
US7008645B2 (en) * | 1998-07-14 | 2006-03-07 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of inhibiting restenosis using bisphosphonates |
US6984400B2 (en) * | 1998-07-14 | 2006-01-10 | Yissum Research Development Company Of The Hebrew University Of Jerusalem | Method of treating restenosis using bisphosphonate nanoparticles |
US6809819B1 (en) | 1999-09-27 | 2004-10-26 | Monsanto Technology Llc | Methods for determining oil in seeds |
US6210611B1 (en) * | 1999-11-30 | 2001-04-03 | Duke University | Methods for producing gas microbubbles having lipid-containing shells formed thereon |
AU3679801A (en) * | 2000-02-08 | 2001-08-20 | Rice University | Optically-active nanoparticles for use in therapeutic and diagnostic methods |
ATE536185T1 (de) * | 2001-03-26 | 2011-12-15 | Dana Farber Cancer Inst Inc | Verfahren zur abschwächung von reaktionen auf hautreizende mittel |
WO2002087543A1 (en) * | 2001-05-01 | 2002-11-07 | Biozone Laboratories, Inc. | Sustained release formulations for nifedipine, dextromethorphan, and danazol |
US20030070679A1 (en) * | 2001-06-01 | 2003-04-17 | Boehringer Ingelheim Pharma Kg | Capsules containing inhalable tiotropium |
US20030044354A1 (en) * | 2001-08-16 | 2003-03-06 | Carpenter Alan P. | Gas microsphere liposome composites for ultrasound imaging and ultrasound stimulated drug release |
US7220239B2 (en) | 2001-12-03 | 2007-05-22 | Ekos Corporation | Catheter with multiple ultrasound radiating members |
US8226629B1 (en) | 2002-04-01 | 2012-07-24 | Ekos Corporation | Ultrasonic catheter power control |
US6921371B2 (en) | 2002-10-14 | 2005-07-26 | Ekos Corporation | Ultrasound radiating members for catheter |
CA2512454C (en) | 2003-02-04 | 2012-10-30 | Bracco Research Sa | Ultrasound contrast agents and process for the preparation thereof |
US20060051407A1 (en) * | 2003-06-27 | 2006-03-09 | Yoram Richter | Method of treating ischemia-reperfusion injury |
US10517883B2 (en) * | 2003-06-27 | 2019-12-31 | Zuli Holdings Ltd. | Method of treating acute myocardial infarction |
EP1701745B1 (en) | 2003-12-22 | 2014-12-10 | Bracco Suisse S.A. | Gas-filled microvesicle assembly for contrast imaging |
US7341569B2 (en) | 2004-01-30 | 2008-03-11 | Ekos Corporation | Treatment of vascular occlusions using ultrasonic energy and microbubbles |
US20080194954A1 (en) * | 2004-06-10 | 2008-08-14 | Imarx Therapeutics, Inc. | Ultrasound Device and Method Using Same |
AU2005273865B2 (en) | 2004-08-18 | 2011-02-24 | Bracco Suisse S.A. | Gas-filled microvesicles composition for contrast imaging |
WO2006110773A2 (en) * | 2005-04-12 | 2006-10-19 | Ekos Corporation | Ultrasound catheter with cavitation promoting surface |
WO2007058668A1 (en) | 2005-11-18 | 2007-05-24 | Imarx Therapeutics, Inc. | Ultrasound apparatus and method to treat an ischemic stroke |
US20070196462A1 (en) * | 2006-01-24 | 2007-08-23 | Imarx Therapeutics, Inc. | Composition and method for neuromuscular blockade |
WO2007127176A2 (en) * | 2006-04-24 | 2007-11-08 | Ekos Corporation | Ultrasound therapy system |
US10182833B2 (en) | 2007-01-08 | 2019-01-22 | Ekos Corporation | Power parameters for ultrasonic catheter |
EP2142167A2 (en) * | 2007-03-30 | 2010-01-13 | Epitarget As | Acoustically sensitive drug delivery particles |
EP2170181B1 (en) | 2007-06-22 | 2014-04-16 | Ekos Corporation | Method and apparatus for treatment of intracranial hemorrhages |
US9044542B2 (en) | 2007-12-21 | 2015-06-02 | Carticept Medical, Inc. | Imaging-guided anesthesia injection systems and methods |
WO2009086182A1 (en) | 2007-12-21 | 2009-07-09 | Carticept Medical, Inc. | Articular injection system |
US8545440B2 (en) | 2007-12-21 | 2013-10-01 | Carticept Medical, Inc. | Injection system for delivering multiple fluids within the anatomy |
WO2011034892A2 (en) * | 2009-09-15 | 2011-03-24 | The Trustees Of Columbia University In The City Of New York | Systems, methods, and devices for microbubbles |
RU2631800C2 (ru) | 2012-04-30 | 2017-09-26 | ДжиИ Хелткер АС | Способ заполнения контейнера вспениваемой композицией |
CN102813942A (zh) * | 2012-08-15 | 2012-12-12 | 钟志容 | 脂质超声微泡介导的腺相关病毒基因转染制剂及制备工艺 |
US9993427B2 (en) | 2013-03-14 | 2018-06-12 | Biorest Ltd. | Liposome formulation and manufacture |
CN113289034A (zh) | 2014-12-31 | 2021-08-24 | 蓝瑟斯医学影像公司 | 脂质封装的气体微球组合物及相关方法 |
CN107708847A (zh) | 2015-04-08 | 2018-02-16 | SonoCore株式会社 | 气泡的制造方法 |
US10656025B2 (en) | 2015-06-10 | 2020-05-19 | Ekos Corporation | Ultrasound catheter |
EP3203256A1 (en) * | 2016-02-02 | 2017-08-09 | B. Braun Melsungen AG | Calibration of mri systems using pre-defined concentrations of 19f isotopes as reference |
EP3452108A4 (en) | 2016-05-04 | 2019-12-25 | Lantheus Medical Imaging, Inc. | METHODS AND DEVICES FOR PREPARING ULTRASONIC CONTRAST AGENTS |
US9789210B1 (en) | 2016-07-06 | 2017-10-17 | Lantheus Medical Imaging, Inc. | Methods for making ultrasound contrast agents |
Family Cites Families (222)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3015128A (en) * | 1960-08-18 | 1962-01-02 | Southwest Res Inst | Encapsulating apparatus |
NL302030A (ja) | 1962-12-21 | 1900-01-01 | ||
US3291843A (en) * | 1963-10-08 | 1966-12-13 | Du Pont | Fluorinated vinyl ethers and their preparation |
BE661981A (ja) * | 1964-04-03 | |||
US3594326A (en) * | 1964-12-03 | 1971-07-20 | Ncr Co | Method of making microscopic capsules |
US3968203A (en) * | 1965-10-01 | 1976-07-06 | Jerome G. Spitzer | Aerosol astringent composition |
US3488714A (en) * | 1966-09-19 | 1970-01-06 | Dow Chemical Co | Formed laminate structure and method of preparation |
US3615972A (en) * | 1967-04-28 | 1971-10-26 | Dow Chemical Co | Expansible thermoplastic polymer particles containing volatile fluid foaming agent and method of foaming the same |
US3532500A (en) * | 1967-07-25 | 1970-10-06 | Eastman Kodak Co | Light sensitive vesicular composition comprising an azido-s-triazine compound |
US3557294A (en) * | 1967-10-12 | 1971-01-19 | Allied Chem | Fluorinated ethers as inhalation convulsants |
US3479811A (en) * | 1967-11-29 | 1969-11-25 | Dow Chemical Co | Yarn and method of making the same |
US3732172A (en) * | 1968-02-28 | 1973-05-08 | Ncr Co | Process for making minute capsules and prefabricated system useful therein |
US3650831A (en) * | 1969-03-10 | 1972-03-21 | Armour Dial Inc | Method of cleaning surfaces |
US4027007A (en) * | 1970-12-09 | 1977-05-31 | Colgate-Palmolive Company | Antiperspirants formulated with borax |
US3873564A (en) * | 1971-03-03 | 1975-03-25 | Synvar Ass | 2-Imidazolinyl-3-oxide-1-oxypropionic acid |
US4108806A (en) * | 1971-12-06 | 1978-08-22 | The Dow Chemical Company | Thermoplastic expandable microsphere process and product |
US4179546A (en) * | 1972-08-28 | 1979-12-18 | The Dow Chemical Company | Method for expanding microspheres and expandable composition |
US3960583A (en) * | 1974-05-02 | 1976-06-01 | Philadelphia Quartz Company | Method of preparing modified hollow, largely spherical particles by spray drying |
CH588887A5 (ja) * | 1974-07-19 | 1977-06-15 | Battelle Memorial Institute | |
US3945956A (en) * | 1975-06-23 | 1976-03-23 | The Dow Chemical Company | Polymerization of styrene acrylonitrile expandable microspheres |
US4138383A (en) * | 1975-11-24 | 1979-02-06 | California Institute Of Technology | Preparation of small bio-compatible microspheres |
GB1523965A (en) * | 1976-03-19 | 1978-09-06 | Ici Ltd | Pharmaceutical compositions containing steroids |
US4162282A (en) * | 1976-04-22 | 1979-07-24 | Coulter Electronics, Inc. | Method for producing uniform particles |
GB1599881A (en) * | 1977-02-02 | 1981-10-07 | Millington A R | Preparation for diagnostic radiology |
CH624011A5 (ja) * | 1977-08-05 | 1981-07-15 | Battelle Memorial Institute | |
CH621479A5 (ja) * | 1977-08-05 | 1981-02-13 | Battelle Memorial Institute | |
US4192859A (en) * | 1978-09-29 | 1980-03-11 | E. R. Squibb & Sons, Inc. | Contrast media containing liposomes as carriers |
US4310506A (en) * | 1979-02-22 | 1982-01-12 | California Institute Of Technology | Means of preparation and applications of liposomes containing high concentrations of entrapped ionic species |
US4276885A (en) * | 1979-05-04 | 1981-07-07 | Rasor Associates, Inc | Ultrasonic image enhancement |
US4265251A (en) * | 1979-06-28 | 1981-05-05 | Rasor Associates, Inc. | Method of determining pressure within liquid containing vessel |
US4310505A (en) * | 1979-11-08 | 1982-01-12 | California Institute Of Technology | Lipid vesicles bearing carbohydrate surfaces as lymphatic directed vehicles for therapeutic and diagnostic substances |
US4342826A (en) * | 1980-02-04 | 1982-08-03 | Collaborative Research, Inc. | Immunoassay products and methods |
US4421562A (en) * | 1980-04-13 | 1983-12-20 | Pq Corporation | Manufacturing process for hollow microspheres |
US4344929A (en) * | 1980-04-25 | 1982-08-17 | Alza Corporation | Method of delivering drug with aid of effervescent activity generated in environment of use |
US4315514A (en) * | 1980-05-08 | 1982-02-16 | William Drewes | Method and apparatus for selective cell destruction |
US4331654A (en) * | 1980-06-13 | 1982-05-25 | Eli Lilly And Company | Magnetically-localizable, biodegradable lipid microspheres |
US4657756A (en) * | 1980-11-17 | 1987-04-14 | Schering Aktiengesellschaft | Microbubble precursors and apparatus for their production and use |
US4442843A (en) * | 1980-11-17 | 1984-04-17 | Schering, Ag | Microbubble precursors and methods for their production and use |
WO1982001642A1 (en) | 1980-11-17 | 1982-05-27 | Med Inc Ultra | Microbubble precursors and methods for their production and use |
US4681119A (en) * | 1980-11-17 | 1987-07-21 | Schering Aktiengesellschaft | Method of production and use of microbubble precursors |
US4427330A (en) * | 1981-03-03 | 1984-01-24 | Carter Charles P | Automatic fence picket stock conveyor for fence picket pointing machine |
US4420442A (en) * | 1981-04-13 | 1983-12-13 | Pq Corporation | Manufacturing process for hollow microspheres |
US4533254A (en) * | 1981-04-17 | 1985-08-06 | Biotechnology Development Corporation | Apparatus for forming emulsions |
EP0068961A3 (fr) * | 1981-06-26 | 1983-02-02 | Thomson-Csf | Dispositif d'échauffement localisé de tissus biologiques |
US4426330A (en) * | 1981-07-20 | 1984-01-17 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US4534899A (en) * | 1981-07-20 | 1985-08-13 | Lipid Specialties, Inc. | Synthetic phospholipid compounds |
US4569836A (en) * | 1981-08-27 | 1986-02-11 | Gordon Robert T | Cancer treatment by intracellular hyperthermia |
EP0088773B1 (en) * | 1981-09-23 | 1987-09-09 | M.B. Fillers Pty. Ltd. | Hollow, bilayered silicate microspheres |
DE3141641A1 (de) * | 1981-10-16 | 1983-04-28 | Schering Ag, 1000 Berlin Und 4619 Bergkamen | Ultraschall-kontrastmittel und dessen herstellung |
BR8107560A (pt) * | 1981-11-19 | 1983-07-05 | Luiz Romariz Duarte | Estimulacao ultra-sonica da consolidacao de fraturas osseas |
US4540629A (en) * | 1982-04-08 | 1985-09-10 | Pq Corporation | Hollow microspheres with organosilicon-silicate walls |
DE3225848A1 (de) * | 1982-07-07 | 1984-01-19 | Schering AG, 1000 Berlin und 4709 Bergkamen | Kortikoidhaltige zubereitung zur topischen applikation |
FR2534487B1 (fr) | 1982-10-15 | 1988-06-10 | Dior Christian Parfums | Procede d'homogeneisation de dispersions de phases lamellaires lipidiques hydratees, et suspensions obtenues par ce procede |
DE3374522D1 (ja) * | 1982-10-26 | 1987-12-23 | University Of Aberdeen | |
US4603044A (en) * | 1983-01-06 | 1986-07-29 | Technology Unlimited, Inc. | Hepatocyte Directed Vesicle delivery system |
US4731239A (en) * | 1983-01-10 | 1988-03-15 | Gordon Robert T | Method for enhancing NMR imaging; and diagnostic use |
US4718433A (en) * | 1983-01-27 | 1988-01-12 | Feinstein Steven B | Contrast agents for ultrasonic imaging |
US4572203A (en) * | 1983-01-27 | 1986-02-25 | Feinstein Steven B | Contact agents for ultrasonic imaging |
US4775522A (en) * | 1983-03-04 | 1988-10-04 | Children's Hospital Research Foundation, A Division Of Children's Hospital Medical Center | NMR compositions for indirectly detecting a dissolved gas in an animal |
US4981692A (en) * | 1983-03-24 | 1991-01-01 | The Liposome Company, Inc. | Therapeutic treatment by intramammary infusion |
US5141738A (en) | 1983-04-15 | 1992-08-25 | Schering Aktiengesellschaft | Ultrasonic contrast medium comprising gas bubbles and solid lipophilic surfactant-containing microparticles and use thereof |
US4544545A (en) * | 1983-06-20 | 1985-10-01 | Trustees University Of Massachusetts | Liposomes containing modified cholesterol for organ targeting |
US4900540A (en) * | 1983-06-20 | 1990-02-13 | Trustees Of The University Of Massachusetts | Lipisomes containing gas for ultrasound detection |
US4615879A (en) * | 1983-11-14 | 1986-10-07 | Vanderbilt University | Particulate NMR contrast agents for gastrointestinal application |
FR2563725B1 (fr) * | 1984-05-03 | 1988-07-15 | Dory Jacques | Appareil d'examen et de localisation de tumeurs par ultrasons muni d'un dispositif de traitement localise par hyperthermie |
JPH0753661B2 (ja) * | 1984-03-08 | 1995-06-07 | フアレス フアーマスーチカル リサーチ エヌブイ | プロ―リポソーム組成物及びリポソームの水性分散物を作る方法 |
GB8407557D0 (en) * | 1984-03-23 | 1984-05-02 | Hayward J A | Polymeric lipsomes |
US4728575A (en) * | 1984-04-27 | 1988-03-01 | Vestar, Inc. | Contrast agents for NMR imaging |
US5008109A (en) * | 1984-05-25 | 1991-04-16 | Vestar, Inc. | Vesicle stabilization |
US5008050A (en) * | 1984-06-20 | 1991-04-16 | The Liposome Company, Inc. | Extrusion technique for producing unilamellar vesicles |
US4620546A (en) * | 1984-06-30 | 1986-11-04 | Kabushiki Kaisha Toshiba | Ultrasound hyperthermia apparatus |
SE8403905D0 (sv) * | 1984-07-30 | 1984-07-30 | Draco Ab | Liposomes and steroid esters |
US4880635B1 (en) * | 1984-08-08 | 1996-07-02 | Liposome Company | Dehydrated liposomes |
US4789501A (en) * | 1984-11-19 | 1988-12-06 | The Curators Of The University Of Missouri | Glass microspheres |
US4921706A (en) * | 1984-11-20 | 1990-05-01 | Massachusetts Institute Of Technology | Unilamellar lipid vesicles and method for their formation |
US4753788A (en) * | 1985-01-31 | 1988-06-28 | Vestar Research Inc. | Method for preparing small vesicles using microemulsification |
US4830858A (en) * | 1985-02-11 | 1989-05-16 | E. R. Squibb & Sons, Inc. | Spray-drying method for preparing liposomes and products produced thereby |
US4689986A (en) * | 1985-03-13 | 1987-09-01 | The University Of Michigan | Variable frequency gas-bubble-manipulating apparatus and method |
US5186922A (en) | 1985-03-15 | 1993-02-16 | See/Shell Biotechnology, Inc. | Use of biodegradable microspheres labeled with imaging energy constrast materials |
US4663161A (en) * | 1985-04-22 | 1987-05-05 | Mannino Raphael J | Liposome methods and compositions |
ATE78158T1 (de) * | 1985-05-22 | 1992-08-15 | Liposome Technology Inc | Verfahren und system zum einatmen von liposomen. |
DE3677112D1 (de) | 1985-08-12 | 1991-02-28 | Battelle Memorial Institute | Poroese filtrierungsglaskugeln und methode zu deren herstellung. |
US4684479A (en) * | 1985-08-14 | 1987-08-04 | Arrigo Joseph S D | Surfactant mixtures, stable gas-in-liquid emulsions, and methods for the production of such emulsions from said mixtures |
US4938947A (en) * | 1985-11-01 | 1990-07-03 | Centre National De La Recherche Scientifique (Cnrs) | Aerosol composition for in vivo imaging |
US4927623A (en) * | 1986-01-14 | 1990-05-22 | Alliance Pharmaceutical Corp. | Dissolution of gas in a fluorocarbon liquid |
US4865836A (en) * | 1986-01-14 | 1989-09-12 | Fluoromed Pharmaceutical, Inc. | Brominated perfluorocarbon emulsions for internal animal use for contrast enhancement and oxygen transport |
US4987154A (en) * | 1986-01-14 | 1991-01-22 | Alliance Pharmaceutical Corp. | Biocompatible, stable and concentrated fluorocarbon emulsions for contrast enhancement and oxygen transport in internal animal use |
EP0231091B1 (en) | 1986-01-24 | 1993-03-31 | Children's Hospital Medical Center | Stable emulsions of highly fluorinated organic compound |
US4737323A (en) * | 1986-02-13 | 1988-04-12 | Liposome Technology, Inc. | Liposome extrusion method |
US4834964A (en) * | 1986-03-07 | 1989-05-30 | M.R.I., Inc. | Use of charged nitroxides as NMR image enhancing agents for CSF |
JPH0751496B2 (ja) * | 1986-04-02 | 1995-06-05 | 武田薬品工業株式会社 | リポソ−ムの製造法 |
DE3614657A1 (de) | 1986-04-30 | 1987-11-05 | Dornier Medizintechnik | Pharmaka enthaltende lipidvesikel, verfahren zu ihrer herstellung und einbringung in den koerper eines lebewesens und freisetzung der in den lipidvesikeln enthaltende pharmaka |
FR2602774B1 (fr) * | 1986-07-29 | 1990-10-19 | Atta | Nouvelles molecules amphiphiles polyhydroxylees et perfluoroalkylees ayant des proprietes tensioactives |
US4728578A (en) * | 1986-08-13 | 1988-03-01 | The Lubrizol Corporation | Compositions containing basic metal salts and/or non-Newtonian colloidal disperse systems and vinyl aromatic containing polymers |
US4776991A (en) * | 1986-08-29 | 1988-10-11 | The United States Of America As Represented By The Secretary Of The Navy | Scaled-up production of liposome-encapsulated hemoglobin |
US4781871A (en) * | 1986-09-18 | 1988-11-01 | Liposome Technology, Inc. | High-concentration liposome processing method |
US4769241A (en) * | 1986-09-23 | 1988-09-06 | Alpha Therapeutic Corporation | Apparatus and process for oxygenation of liquid state dissolved oxygen-carrying formulation |
ZW11287A1 (en) * | 1986-11-04 | 1989-01-25 | Aeci Ltd | Process for the production of an explosive |
DE3637926C1 (de) | 1986-11-05 | 1987-11-26 | Schering Ag | Ultraschall-Manometrieverfahren in einer Fluessigkeit mittels Mikroblaeschen |
US5049388A (en) * | 1986-11-06 | 1991-09-17 | Research Development Foundation | Small particle aerosol liposome and liposome-drug combinations for medical use |
US4863717A (en) * | 1986-11-10 | 1989-09-05 | The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The University Of Oregon | Methods for circumventing the problem of free radial reduction associated with the use of stable nitroxide free radicals as contrast agents for magnetic reasonance imaging |
US4933121A (en) * | 1986-12-10 | 1990-06-12 | Ciba Corning Diagnostics Corp. | Process for forming liposomes |
DK175531B1 (da) | 1986-12-15 | 2004-11-22 | Nexstar Pharmaceuticals Inc | Leveringsvehikel med amphiphil-associeret aktiv bestanddel |
US5089181A (en) * | 1987-02-24 | 1992-02-18 | Vestar, Inc. | Method of dehydrating vesicle preparations for long term storage |
CA1321048C (en) * | 1987-03-05 | 1993-08-10 | Robert W. J. Lencki | Microspheres and method of producing same |
US5219538A (en) | 1987-03-13 | 1993-06-15 | Micro-Pak, Inc. | Gas and oxygen carrying lipid vesicles |
US5000960A (en) * | 1987-03-13 | 1991-03-19 | Micro-Pak, Inc. | Protein coupling to lipid vesicles |
ES2026257T3 (es) * | 1987-06-23 | 1992-04-16 | Hafslund Nycomed Innovation Ab | Mejoras introducidas en la presentacion de imagenes por resonancia magnetica nuclear. |
US5354549A (en) | 1987-07-24 | 1994-10-11 | Nycomed Imaging As | Iodinated esters |
US4844882A (en) * | 1987-12-29 | 1989-07-04 | Molecular Biosystems, Inc. | Concentrated stabilized microbubble-type ultrasonic imaging agent |
IE61591B1 (en) | 1987-12-29 | 1994-11-16 | Molecular Biosystems Inc | Concentrated stabilized microbubble-type ultrasonic imaging agent and method of production |
WO1989006978A1 (en) | 1988-02-05 | 1989-08-10 | Schering Aktiengesellschaft Berlin Und Bergkamen | Ultrasonic contrast agents, process for producing them and their use as diagnostic and therapeutic agents |
US5425366A (en) | 1988-02-05 | 1995-06-20 | Schering Aktiengesellschaft | Ultrasonic contrast agents for color Doppler imaging |
US4898734A (en) * | 1988-02-29 | 1990-02-06 | Massachusetts Institute Of Technology | Polymer composite for controlled release or membrane formation |
DE3812816A1 (de) | 1988-04-16 | 1989-11-02 | Lawaczeck Ruediger Dipl Phys P | Verfahren zur solubilisierung von liposomen und/oder biologischer membranen sowie deren verwendung |
US5171755A (en) | 1988-04-29 | 1992-12-15 | Hemagen/Pfc | Emulsions of highly fluorinated organic compounds |
US4893624A (en) * | 1988-06-21 | 1990-01-16 | Massachusetts Institute Of Technology | Diffuse focus ultrasound hyperthermia system |
US4993415A (en) * | 1988-08-19 | 1991-02-19 | Alliance Pharmaceutical Corp. | Magnetic resonance imaging with perfluorocarbon hydrides |
US4996041A (en) * | 1988-08-19 | 1991-02-26 | Toshiyuki Arai | Method for introducing oxygen-17 into tissue for imaging in a magnetic resonance imaging system |
DE3828905A1 (de) | 1988-08-23 | 1990-03-15 | Schering Ag | Mittel bestehend aus cavitate oder clathrate bildenden wirt/gast-komplexen als kontrastmittel |
US5045304A (en) * | 1988-08-31 | 1991-09-03 | Wayne State University | Contras agent having an imaging agent coupled to viable granulocytes for use in magnetic resonance imaging of abscess and a method of preparing and using same |
US5410516A (en) | 1988-09-01 | 1995-04-25 | Schering Aktiengesellschaft | Ultrasonic processes and circuits for performing them |
US4957656A (en) * | 1988-09-14 | 1990-09-18 | Molecular Biosystems, Inc. | Continuous sonication method for preparing protein encapsulated microbubbles |
IL91664A (en) | 1988-09-28 | 1993-05-13 | Yissum Res Dev Co | Ammonium transmembrane gradient system for efficient loading of liposomes with amphipathic drugs and their controlled release |
FR2637182B1 (fr) | 1988-10-03 | 1992-11-06 | Lvmh Rech | Compositions a base de phases lamellaires lipidiques hydratees ou de liposomes contenant un ecdysteroide, de preference l'ecdysterone, ou l'un de ses derives; et compositions cosmetiques, pharmaceutiques, notamment dermatologiques, de sericulture ou phytosanitaires l'incorporant |
US5114703A (en) * | 1989-05-30 | 1992-05-19 | Alliance Pharmaceutical Corp. | Percutaneous lymphography using particulate fluorocarbon emulsions |
JP2849471B2 (ja) | 1989-06-22 | 1999-01-20 | アライアンス ファーマシューティカル コーポレイション | 界面活性剤の性質を有するフッ素およびリン含有両親媒性分子 |
US5019370A (en) * | 1989-07-10 | 1991-05-28 | University Of Kentucky Research Foundation | Biodegradable, low biological toxicity radiographic contrast medium and method of x-ray imaging |
US5194266A (en) | 1989-08-08 | 1993-03-16 | Liposome Technology, Inc. | Amphotericin B/cholesterol sulfate composition and method |
US5562608A (en) | 1989-08-28 | 1996-10-08 | Biopulmonics, Inc. | Apparatus for pulmonary delivery of drugs with simultaneous liquid lavage and ventilation |
US5620689A (en) | 1989-10-20 | 1997-04-15 | Sequus Pharmaceuuticals, Inc. | Liposomes for treatment of B-cell and T-cell disorders |
US5013556A (en) * | 1989-10-20 | 1991-05-07 | Liposome Technology, Inc. | Liposomes with enhanced circulation time |
US5334381A (en) | 1989-12-22 | 1994-08-02 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5469854A (en) | 1989-12-22 | 1995-11-28 | Imarx Pharmaceutical Corp. | Methods of preparing gas-filled liposomes |
US5149319A (en) | 1990-09-11 | 1992-09-22 | Unger Evan C | Methods for providing localized therapeutic heat to biological tissues and fluids |
US5776429A (en) * | 1989-12-22 | 1998-07-07 | Imarx Pharmaceutical Corp. | Method of preparing gas-filled microspheres using a lyophilized lipids |
US5922304A (en) * | 1989-12-22 | 1999-07-13 | Imarx Pharmaceutical Corp. | Gaseous precursor filled microspheres as magnetic resonance imaging contrast agents |
US5209720A (en) | 1989-12-22 | 1993-05-11 | Unger Evan C | Methods for providing localized therapeutic heat to biological tissues and fluids using gas filled liposomes |
US5585112A (en) | 1989-12-22 | 1996-12-17 | Imarx Pharmaceutical Corp. | Method of preparing gas and gaseous precursor-filled microspheres |
US5230882A (en) | 1989-12-22 | 1993-07-27 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5542935A (en) | 1989-12-22 | 1996-08-06 | Imarx Pharmaceutical Corp. | Therapeutic delivery systems related applications |
US5123414A (en) * | 1989-12-22 | 1992-06-23 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5088499A (en) * | 1989-12-22 | 1992-02-18 | Unger Evan C | Liposomes as contrast agents for ultrasonic imaging and methods for preparing the same |
US5305757A (en) | 1989-12-22 | 1994-04-26 | Unger Evan C | Gas filled liposomes and their use as ultrasonic contrast agents |
US5228446A (en) | 1989-12-22 | 1993-07-20 | Unger Evan C | Gas filled liposomes and their use as ultrasonic contrast agents |
US5733572A (en) * | 1989-12-22 | 1998-03-31 | Imarx Pharmaceutical Corp. | Gas and gaseous precursor filled microspheres as topical and subcutaneous delivery vehicles |
US5352435A (en) | 1989-12-22 | 1994-10-04 | Unger Evan C | Ionophore containing liposomes for ultrasound imaging |
US5773024A (en) * | 1989-12-22 | 1998-06-30 | Imarx Pharmaceutical Corp. | Container with multi-phase composition for use in diagnostic and therapeutic applications |
DE4004430A1 (de) | 1990-02-09 | 1991-08-14 | Schering Ag | Aus polyaldehyden aufgebaute kontrastmittel |
US5578292A (en) | 1991-11-20 | 1996-11-26 | Bracco International B.V. | Long-lasting aqueous dispersions or suspensions of pressure-resistant gas-filled microvesicles and methods for the preparation thereof |
US5556610A (en) | 1992-01-24 | 1996-09-17 | Bracco Research S.A. | Gas mixtures useful as ultrasound contrast media, contrast agents containing the media and method |
IN172208B (ja) | 1990-04-02 | 1993-05-01 | Sint Sa | |
US5445813A (en) | 1992-11-02 | 1995-08-29 | Bracco International B.V. | Stable microbubble suspensions as enhancement agents for ultrasound echography |
US5672585A (en) | 1990-04-06 | 1997-09-30 | La Jolla Cancer Research Foundation | Method and composition for treating thrombosis |
US5358702A (en) | 1990-04-10 | 1994-10-25 | Unger Evan C | Methoxylated gel particle contrast media for improved diagnostic imaging |
US5078994A (en) * | 1990-04-12 | 1992-01-07 | Eastman Kodak Company | Microgel drug delivery system |
JPH03297475A (ja) | 1990-04-16 | 1991-12-27 | Ken Ishihara | 共振音波により薬物の放出を制御する方法 |
US5190982A (en) | 1990-04-26 | 1993-03-02 | Hoechst Aktiengesellschaft | Ultrasonic contrast agents, processes for their preparation and the use thereof as diagnostic and therapeutic agents |
US5205287A (en) | 1990-04-26 | 1993-04-27 | Hoechst Aktiengesellschaft | Ultrasonic contrast agents, processes for their preparation and the use thereof as diagnostic and therapeutic agents |
US5137928A (en) * | 1990-04-26 | 1992-08-11 | Hoechst Aktiengesellschaft | Ultrasonic contrast agents, processes for their preparation and the use thereof as diagnostic and therapeutic agents |
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 |
US5196348A (en) | 1990-06-11 | 1993-03-23 | Air Products And Chemicals, Inc. | Perfluoro-crown ethers in fluorine magnetic resonance spectroscopy of biopsied tissue |
US5315997A (en) | 1990-06-19 | 1994-05-31 | Molecular Biosystems, Inc. | Method of magnetic resonance imaging using diamagnetic contrast |
US5215680A (en) | 1990-07-10 | 1993-06-01 | Cavitation-Control Technology, Inc. | Method for the production of medical-grade lipid-coated microbubbles, paramagnetic labeling of such microbubbles and therapeutic uses of microbubbles |
IL95743A (en) | 1990-09-19 | 1993-02-21 | Univ Ramot | Method of measuring blood flow |
CA2068334C (en) | 1990-10-05 | 1996-09-03 | Claude Giddey | Method for the preparation of stable suspensions of hollow gas-filled microspheres suitable for ultrasonic echography |
US5487390A (en) | 1990-10-05 | 1996-01-30 | Massachusetts Institute Of Technology | Gas-filled polymeric microbubbles for ultrasound imaging |
CA2098849C (en) | 1990-12-20 | 2007-07-10 | Ralph R. Weichselbaum | Control of gene expression by ionizing radiation |
US5107842A (en) | 1991-02-22 | 1992-04-28 | Molecular Biosystems, Inc. | Method of ultrasound imaging of the gastrointestinal tract |
EP0504881B2 (en) | 1991-03-22 | 2000-11-08 | Katsuro Tachibana | Booster for therapy of diseases with ultrasound and pharmaceutical liquid composition containing the same |
GB9106673D0 (en) | 1991-03-28 | 1991-05-15 | Hafslund Nycomed As | Improvements in or relating to contrast agents |
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 |
US5874062A (en) * | 1991-04-05 | 1999-02-23 | Imarx Pharmaceutical Corp. | Methods of computed tomography using perfluorocarbon gaseous filled microspheres as contrast agents |
US5496535A (en) | 1991-04-12 | 1996-03-05 | Alliance Pharmaceutical Corp. | Fluorocarbon contrast media for use with MRI and radiographic imaging |
US5147631A (en) | 1991-04-30 | 1992-09-15 | Du Pont Merck Pharmaceutical Company | Porous inorganic ultrasound contrast agents |
US5558857A (en) | 1991-06-03 | 1996-09-24 | Nycomed Imaging As | Contrast agents |
GB9116610D0 (en) | 1991-08-01 | 1991-09-18 | Danbiosyst Uk | Preparation of microparticles |
US5409688A (en) | 1991-09-17 | 1995-04-25 | Sonus Pharmaceuticals, Inc. | Gaseous ultrasound contrast media |
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 |
RU2114637C1 (ru) | 1991-09-17 | 1998-07-10 | Сонус Фармасьютикалз, Инк. | Биосовместимая контрастная среда и способ получения ультразвукового изображения |
US5362477A (en) | 1991-10-25 | 1994-11-08 | Mallinckrodt Medical, Inc. | 19F magnetic resonance imaging agents which include a nitroxide moiety |
US5196183A (en) | 1991-12-04 | 1993-03-23 | Sterling Winthrop Inc. | Contrast agents for ultrasound imaging |
GB9200388D0 (en) | 1992-01-09 | 1992-02-26 | Nycomed As | Improvements in or relating to contrast agents |
GB9200387D0 (en) | 1992-01-09 | 1992-02-26 | Nycomed As | Improvements in or relating to contrast agents |
IL104084A (en) | 1992-01-24 | 1996-09-12 | Bracco Int Bv | Sustainable aqueous suspensions of pressure-resistant and gas-filled blisters, their preparation, and contrast agents containing them |
US5470582A (en) | 1992-02-07 | 1995-11-28 | Syntex (U.S.A.) Inc. | Controlled delivery of pharmaceuticals from preformed porous polymeric microparticles |
JP3325300B2 (ja) | 1992-02-28 | 2002-09-17 | 株式会社東芝 | 超音波治療装置 |
US5247935A (en) | 1992-03-19 | 1993-09-28 | General Electric Company | Magnetic resonance guided focussed ultrasound surgery |
WO1993020802A1 (en) | 1992-04-09 | 1993-10-28 | Northwestern University | Acoustically reflective liposomes and methods to make and use the same |
US5858399A (en) | 1992-04-09 | 1999-01-12 | Northwestern University | Acoustically reflective liposomes and methods to make and use the same |
US5339814A (en) | 1992-04-14 | 1994-08-23 | Lasker Sigmund E | Process for visualizing tissue metabolism using oxygen-17 |
US5846516A (en) | 1992-06-03 | 1998-12-08 | Alliance Pharmaceutial Corp. | Perfluoroalkylated amphiphilic phosphorus compounds: preparation and biomedical applications |
DE4221256C2 (de) | 1992-06-26 | 1997-07-10 | Lancaster Group Ag | Galenische Zusammensetzung für die topische Anwendung |
US5552155A (en) | 1992-12-04 | 1996-09-03 | The Liposome Company, Inc. | Fusogenic lipsomes and methods for making and using same |
CZ191695A3 (en) | 1993-01-25 | 1996-05-15 | Sonus Pharma Inc | Biologically compatible contrast agent, process of its preparation and representation method by ultrasound |
US5558855A (en) | 1993-01-25 | 1996-09-24 | Sonus Pharmaceuticals | Phase shift colloids as ultrasound contrast agents |
FR2700952B1 (fr) | 1993-01-29 | 1995-03-17 | Oreal | Nouvelles compositions cosmétiques ou dermopharmaceutiques sous forme de gels aqueux modifiés par addition de microsphères expansées. |
US5362478A (en) | 1993-03-26 | 1994-11-08 | Vivorx Pharmaceuticals, Inc. | Magnetic resonance imaging with fluorocarbons encapsulated in a cross-linked polymeric shell |
EP0693924B2 (en) | 1993-02-22 | 2008-04-09 | Abraxis BioScience, Inc. | Methods for (in vivo) delivery of biologics and compositions useful therefor |
US5716597A (en) | 1993-06-04 | 1998-02-10 | Molecular Biosystems, Inc. | Emulsions as contrast agents and method of use |
BR9406993A (pt) | 1993-07-02 | 1996-09-10 | Molecular Biosystems Inc | Microesferas de gases insolúveis encapsulados com proteína e sua preparação e uso como agentes de imagem ultrassônica |
US5855865A (en) | 1993-07-02 | 1999-01-05 | Molecular Biosystems, Inc. | Method for making encapsulated gas microspheres from heat denatured protein in the absence of oxygen gas |
US5565215A (en) | 1993-07-23 | 1996-10-15 | Massachusettes Institute Of Technology | Biodegradable injectable particles for imaging |
PT711179E (pt) | 1993-07-30 | 2005-03-31 | Imcor Pharmaceutical Company | Composicoes de microbolhas estabilizadas para ultra-som |
US5433204A (en) | 1993-11-16 | 1995-07-18 | Camilla Olson | Method of assessing placentation |
CN1148812A (zh) | 1994-03-28 | 1997-04-30 | 尼科梅德成像有限公司 | “脂质体” |
US5545396A (en) | 1994-04-08 | 1996-08-13 | The Research Foundation Of State University Of New York | Magnetic resonance imaging using hyperpolarized noble gases |
WO1995029705A1 (en) | 1994-05-03 | 1995-11-09 | Molecular Biosystems, Inc. | Composition for ultrasonically quantitating myocardial perfusion |
US5571797A (en) | 1994-05-11 | 1996-11-05 | Arch Development Corporation | Method of inducing gene expression by ionizing radiation |
US5502094A (en) | 1994-05-20 | 1996-03-26 | Minnesota Mining And Manufacturing Company | Physiologically acceptable emulsions containing perfluorocarbon ether hydrides and methods for use |
US5562893A (en) | 1994-08-02 | 1996-10-08 | Molecular Biosystems, Inc. | Gas-filled microspheres with fluorine-containing shells |
US5540909A (en) | 1994-09-28 | 1996-07-30 | Alliance Pharmaceutical Corp. | Harmonic ultrasound imaging with microbubbles |
US5569448A (en) | 1995-01-24 | 1996-10-29 | Nano Systems L.L.C. | Sulfated nonionic block copolymer surfactants as stabilizer coatings for nanoparticle compositions |
US5556372A (en) | 1995-02-15 | 1996-09-17 | Exogen, Inc. | Apparatus for ultrasonic bone treatment |
US5560364A (en) | 1995-05-12 | 1996-10-01 | The Board Of Regents Of The University Of Nebraska | Suspended ultra-sound induced microbubble cavitation imaging |
US5558092A (en) | 1995-06-06 | 1996-09-24 | Imarx Pharmaceutical Corp. | Methods and apparatus for performing diagnostic and therapeutic ultrasound simultaneously |
US5804162A (en) | 1995-06-07 | 1998-09-08 | Alliance Pharmaceutical Corp. | Gas emulsions stabilized with fluorinated ethers having low Ostwald coefficients |
US5606973A (en) | 1995-06-07 | 1997-03-04 | Molecular Biosystems, Inc. | Liquid core microdroplets for ultrasound imaging |
CA2218541A1 (en) * | 1995-06-07 | 1996-12-19 | Imarx Pharmaceutical Corp. | Novel targeted compositions for diagnostic and therapeutic use |
US5840023A (en) | 1996-01-31 | 1998-11-24 | Oraevsky; Alexander A. | Optoacoustic imaging for medical diagnosis |
JP2001507207A (ja) * | 1996-05-01 | 2001-06-05 | イマアーレクス・フアーマシユーチカル・コーポレーシヨン | 化合物を細胞に送達する方法 |
-
1996
- 1996-04-30 US US08/643,070 patent/US5776429A/en not_active Expired - Lifetime
-
1997
- 1997-04-02 WO PCT/US1997/005908 patent/WO1997040858A1/en not_active Application Discontinuation
- 1997-04-02 CN CN97194256A patent/CN1216925A/zh active Pending
- 1997-04-02 AU AU24510/97A patent/AU2451097A/en not_active Abandoned
- 1997-04-02 JP JP09538909A patent/JP2000510108A/ja not_active Ceased
- 1997-04-02 EP EP97920281A patent/EP0923383A4/en not_active Withdrawn
-
1998
- 1998-02-19 US US09/026,326 patent/US6033646A/en not_active Expired - Lifetime
-
2008
- 2008-06-04 JP JP2008146776A patent/JP2008260775A/ja active Pending
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008526785A (ja) * | 2005-01-10 | 2008-07-24 | チョンチン・ハイフ(エイチアイエフユー)・テクノロジー・カンパニー・リミテッド | 高密度焦点式超音波療法のための増強剤および同剤のスクリーニングの方法 |
JP4773458B2 (ja) * | 2005-01-10 | 2011-09-14 | チョンチン・ハイフ(エイチアイエフユー)・テクノロジー・カンパニー・リミテッド | 高密度焦点式超音波療法のための増強剤および同剤のスクリーニングの方法 |
Also Published As
Publication number | Publication date |
---|---|
EP0923383A1 (en) | 1999-06-23 |
EP0923383A4 (en) | 2001-06-13 |
US6033646A (en) | 2000-03-07 |
AU2451097A (en) | 1997-11-19 |
US5776429A (en) | 1998-07-07 |
WO1997040858A1 (en) | 1997-11-06 |
JP2008260775A (ja) | 2008-10-30 |
CN1216925A (zh) | 1999-05-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2000510108A (ja) | 新規な分散性脂質配合物及びそれらの使用 | |
KR100500334B1 (ko) | 조영제또는그와관련된개선 | |
DE69632907T2 (de) | Neue zusammensetzungen von lipiden und stabilisierenden materialen | |
JP4229918B2 (ja) | 超音波のコントラスト増強のためのリン脂質を含む安定な気体エマルジョン | |
DE69433723T2 (de) | Verfahren für die in-vivo-verabreichung von biologischen substanzen und hierfür verwendbare zusammensetzungen | |
DE69831755T2 (de) | Optoakustische kontrastmittel und anwendungsverfahren | |
US5531980A (en) | Stable microbubbles suspensions injectable into living organisms | |
JP3135919B2 (ja) | 超音波検査法のための強化剤としての安定性微小泡懸濁液 | |
DE69432358T2 (de) | Gashaltige mikrosphären zur topischen und subkutanen anwendung | |
JP4670083B2 (ja) | 超音波造影剤およびその製造方法 | |
US6599527B1 (en) | Preparation of pharmaceutical compositions | |
KR100416163B1 (ko) | 마이크로캡슐,그제조방법및용도 | |
JP2001514615A (ja) | 生物活性剤の送達方法 | |
Bhaskaran et al. | Comparative evaluation of niosome formulations prepared by different techniques | |
JP2001524983A (ja) | 新規の音響活性薬剤輸送系 | |
MXPA04012567A (es) | Nanocapsulas lipidicas encubiertas, metodos para la preparacion de las mismas y uso de las mismas como un portador para principios activos. | |
CN107427482A (zh) | 凝血酸的多囊脂质体制剂 | |
FR2840532A1 (fr) | Nanocapsules lipidiques furtives, procede de preparation et utilisation comme vecteur de principes(s) actif(s) | |
HU217121B (hu) | Gáztartalmú mikroszemcsék és ezeket tartalmazó ultrahang kontrasztanyagok | |
JPH03504382A (ja) | 高比率活性剤:脂質複合体 | |
JPWO2003015753A1 (ja) | リポソーム製剤 | |
WO2006076826A1 (fr) | Composition de contraste pour ultrasons utilisant un phospholipide filmogene et procede de preparation de celle-ci | |
KR20050020988A (ko) | 스텔스 지질 나노캡슐, 이의 제조 방법, 및 유효성분(들)을 위한 담체로서 이의 용도 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20040401 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20040401 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20071204 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080304 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080414 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080331 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080512 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20080430 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20080616 |
|
A313 | Final decision of rejection without a dissenting response from the applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A313 Effective date: 20080715 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20080909 |