NL9201722A - Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan. - Google Patents

Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan. Download PDF

Info

Publication number: NL9201722A
Authority: NL; Netherlands
Prior art keywords: plasminogen; liposomes; composition; activator; plasminogen activator
Prior art date: 1992-10-05

Application number

NL9201722A

Other languages

English (en)

Dutch (nl)

Original Assignee

Stichting Tech Wetenschapp

Priority date (The priority date 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 date listed.)

1992-10-05

Filing date

1992-10-05

Publication date

1994-05-02

1992-10-05 Application filed by Stichting Tech Wetenschapp filed Critical Stichting Tech Wetenschapp

1992-10-05 Priority to NL9201722A priority Critical patent/NL9201722A/nl

1993-10-05 Priority to PCT/NL1993/000195 priority patent/WO1994007537A1/en

1993-10-05 Priority to DE69321131T priority patent/DE69321131D1/de

1993-10-05 Priority to JP6508918A priority patent/JPH08502060A/ja

1993-10-05 Priority to EP93923685A priority patent/EP0662841B1/de

1993-10-05 Priority to AU53454/94A priority patent/AU5345494A/en

1993-10-05 Priority to CA002146324A priority patent/CA2146324A1/en

1993-10-05 Priority to AT93923685T priority patent/ATE171073T1/de

1994-05-02 Publication of NL9201722A publication Critical patent/NL9201722A/nl

1995-03-30 Priority to NO951219A priority patent/NO951219L/no

Links

238000000034 method Methods 0.000 title claims abstract description 37
102000004169 proteins and genes Human genes 0.000 title claims abstract description 35
108090000623 proteins and genes Proteins 0.000 title claims abstract description 35
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 13
238000002360 preparation method Methods 0.000 title claims abstract description 12
102000013566 Plasminogen Human genes 0.000 claims abstract description 100
108010051456 Plasminogen Proteins 0.000 claims abstract description 100
239000002502 liposome Substances 0.000 claims abstract description 99
102000001938 Plasminogen Activators Human genes 0.000 claims abstract description 48
108010001014 Plasminogen Activators Proteins 0.000 claims abstract description 48
229940127126 plasminogen activator Drugs 0.000 claims abstract description 48
239000000203 mixture Substances 0.000 claims abstract description 38
102000009123 Fibrin Human genes 0.000 claims abstract description 22
108010073385 Fibrin Proteins 0.000 claims abstract description 22
BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims abstract description 22
208000007536 Thrombosis Diseases 0.000 claims abstract description 22
229950003499 fibrin Drugs 0.000 claims abstract description 22
102000003978 Tissue Plasminogen Activator Human genes 0.000 claims abstract description 15
108090000373 Tissue Plasminogen Activator Proteins 0.000 claims abstract description 15
230000003993 interaction Effects 0.000 claims abstract description 10
229940039227 diagnostic agent Drugs 0.000 claims abstract description 5
239000000032 diagnostic agent Substances 0.000 claims abstract description 5
235000018102 proteins Nutrition 0.000 claims description 33
229960000187 tissue plasminogen activator Drugs 0.000 claims description 14
238000006243 chemical reaction Methods 0.000 claims description 11
-1 cysteine Chemical class 0.000 claims description 10
150000003904 phospholipids Chemical class 0.000 claims description 10
230000027455 binding Effects 0.000 claims description 9
125000003396 thiol group Chemical class [H]S* 0.000 claims description 9
239000003814 drug Substances 0.000 claims description 7
150000003141 primary amines Chemical class 0.000 claims description 7
239000012190 activator Substances 0.000 claims description 5
229940079593 drug Drugs 0.000 claims description 4
238000010257 thawing Methods 0.000 claims description 4
239000002577 cryoprotective agent Substances 0.000 claims description 3
230000008569 process Effects 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 2
XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 2
235000018417 cysteine Nutrition 0.000 claims description 2
229910001507 metal halide Inorganic materials 0.000 claims description 2
150000005309 metal halides Chemical class 0.000 claims description 2
238000000926 separation method Methods 0.000 claims description 2
230000001747 exhibiting effect Effects 0.000 claims 1
230000008685 targeting Effects 0.000 abstract description 2
238000001514 detection method Methods 0.000 abstract 1
239000007858 starting material Substances 0.000 abstract 1
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
230000000694 effects Effects 0.000 description 9
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
239000000872 buffer Substances 0.000 description 8
230000002537 thrombolytic effect Effects 0.000 description 7
238000005859 coupling reaction Methods 0.000 description 6
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 5
239000007995 HEPES buffer Substances 0.000 description 5
239000003795 chemical substances by application Substances 0.000 description 5
230000008878 coupling Effects 0.000 description 5
238000010168 coupling process Methods 0.000 description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
239000004698 Polyethylene Substances 0.000 description 4
239000003146 anticoagulant agent Substances 0.000 description 4
239000011780 sodium chloride Substances 0.000 description 4
239000000243 solution Substances 0.000 description 4
238000005199 ultracentrifugation Methods 0.000 description 4
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
108010023197 Streptokinase Proteins 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
125000003277 amino group Chemical group 0.000 description 3
230000015556 catabolic process Effects 0.000 description 3
238000006731 degradation reaction Methods 0.000 description 3
238000005538 encapsulation Methods 0.000 description 3
238000011534 incubation Methods 0.000 description 3
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
229920000053 polysorbate 80 Polymers 0.000 description 3
229960005202 streptokinase Drugs 0.000 description 3
SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 2
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
229920001213 Polysorbate 20 Polymers 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
230000004913 activation Effects 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
229960002684 aminocaproic acid Drugs 0.000 description 2
230000015572 biosynthetic process 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
239000000306 component Substances 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
125000004356 hydroxy functional group Chemical group O* 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000011068 loading method Methods 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
229940012957 plasmin Drugs 0.000 description 2
235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
239000000843 powder Substances 0.000 description 2
238000000746 purification Methods 0.000 description 2
239000000758 substrate Substances 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 1
208000031104 Arterial Occlusive disease Diseases 0.000 description 1
108090001008 Avidin Proteins 0.000 description 1
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
206010051055 Deep vein thrombosis Diseases 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
108010049003 Fibrinogen Proteins 0.000 description 1
102000008946 Fibrinogen Human genes 0.000 description 1
SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
229930186217 Glycolipid Natural products 0.000 description 1
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 1
AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
239000000232 Lipid Bilayer Substances 0.000 description 1
229930195725 Mannitol Natural products 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 1
HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 1
AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
208000010378 Pulmonary Embolism Diseases 0.000 description 1
101710145796 Staphylokinase Proteins 0.000 description 1
229930182558 Sterol Natural products 0.000 description 1
108090000190 Thrombin Proteins 0.000 description 1
239000007983 Tris buffer Substances 0.000 description 1
108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
206010047249 Venous thrombosis Diseases 0.000 description 1
ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 description 1
206010000891 acute myocardial infarction Diseases 0.000 description 1
AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
239000002246 antineoplastic agent Substances 0.000 description 1
239000012736 aqueous medium Substances 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
208000021328 arterial occlusion Diseases 0.000 description 1
230000008901 benefit Effects 0.000 description 1
230000008033 biological extinction Effects 0.000 description 1
229960002685 biotin Drugs 0.000 description 1
239000011616 biotin Substances 0.000 description 1
108091006004 biotinylated proteins Proteins 0.000 description 1
230000000740 bleeding effect Effects 0.000 description 1
239000008280 blood Substances 0.000 description 1
210000004369 blood Anatomy 0.000 description 1
239000012503 blood component Substances 0.000 description 1
230000037396 body weight Effects 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
239000000969 carrier Substances 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
235000012000 cholesterol Nutrition 0.000 description 1
230000001684 chronic effect Effects 0.000 description 1
230000002301 combined effect Effects 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
230000001268 conjugating effect Effects 0.000 description 1
239000000356 contaminant Substances 0.000 description 1
210000004351 coronary vessel Anatomy 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000006196 deacetylation Effects 0.000 description 1
238000003381 deacetylation reaction Methods 0.000 description 1
238000001212 derivatisation Methods 0.000 description 1
230000001687 destabilization Effects 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
239000006185 dispersion Substances 0.000 description 1
230000006334 disulfide bridging Effects 0.000 description 1
238000002296 dynamic light scattering Methods 0.000 description 1
230000002500 effect on skin Effects 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
229940088598 enzyme Drugs 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000001125 extrusion Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229940012952 fibrinogen Drugs 0.000 description 1
239000012467 final product Substances 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
230000006870 function Effects 0.000 description 1
238000002523 gelfiltration Methods 0.000 description 1
230000003862 health status Effects 0.000 description 1
230000023597 hemostasis Effects 0.000 description 1
230000002163 immunogen Effects 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
238000001361 intraarterial administration Methods 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
238000007912 intraperitoneal administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
230000007774 longterm Effects 0.000 description 1
125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
108010087750 lysyl-plasminogen Proteins 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
239000000463 material Substances 0.000 description 1
230000001404 mediated effect Effects 0.000 description 1
239000012528 membrane Substances 0.000 description 1
239000003094 microcapsule Substances 0.000 description 1
108010049112 miniplasminogen Proteins 0.000 description 1
239000000178 monomer Substances 0.000 description 1
208000010125 myocardial infarction Diseases 0.000 description 1
230000009871 nonspecific binding Effects 0.000 description 1
229960003104 ornithine Drugs 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
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 description 1
230000004962 physiological condition Effects 0.000 description 1
230000033885 plasminogen activation Effects 0.000 description 1
229920000515 polycarbonate Polymers 0.000 description 1
239000004417 polycarbonate Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
239000011148 porous material Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
239000000047 product Substances 0.000 description 1
239000011814 protection agent Substances 0.000 description 1
238000001742 protein purification Methods 0.000 description 1
239000012460 protein solution Substances 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
150000003839 salts Chemical class 0.000 description 1
108010073863 saruplase Proteins 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
150000003432 sterols Chemical class 0.000 description 1
235000003702 sterols Nutrition 0.000 description 1
108010008962 streptokinase-plasminogen complex Proteins 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
238000005636 thioacylation reaction Methods 0.000 description 1
238000006177 thiolation reaction Methods 0.000 description 1
229960004072 thrombin Drugs 0.000 description 1
230000009424 thromboembolic effect Effects 0.000 description 1
229960000103 thrombolytic agent Drugs 0.000 description 1
LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
229960005356 urokinase Drugs 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
235000005074 zinc chloride Nutrition 0.000 description 1
239000011592 zinc chloride Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
- A61K38/49—Urokinase; Tissue plasminogen activator
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/69—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
- A61K47/6905—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion
- A61K47/6911—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit the form being a colloid or an emulsion the form being a liposome
- 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—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- A61K9/1271—Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Landscapes

Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Epidemiology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Dispersion Chemistry (AREA)
Hematology (AREA)
Gastroenterology & Hepatology (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Diabetes (AREA)
Biomedical Technology (AREA)
Chemical Kinetics & Catalysis (AREA)
Immunology (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Medicinal Preparation (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Investigating Or Analysing Biological Materials (AREA)
Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Actuator (AREA)
Structures Of Non-Positive Displacement Pumps (AREA)

NL9201722A 1992-10-05 1992-10-05 Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan. NL9201722A (nl)

Priority Applications (9)

Application Number	Priority Date	Filing Date	Title
NL9201722A NL9201722A (nl)	1992-10-05	1992-10-05	Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan.
PCT/NL1993/000195 WO1994007537A1 (en)	1992-10-05	1993-10-05	Pharmaceutical composition for site-specific release of a clot-dissolving protein
DE69321131T DE69321131D1 (de)	1992-10-05	1993-10-05	Pharmazeutische zusammensetzung für ortsspezifische abgabe von blutgerinselauflösende proteine
JP6508918A JPH08502060A (ja)	1992-10-05	1993-10-05	血餅−溶解タンパク質の部位−特異的放出用医薬組成物
EP93923685A EP0662841B1 (de)	1992-10-05	1993-10-05	Pharmazeutische zusammensetzung für ortsspezifische abgabe von blutgerinselauflösende proteine
AU53454/94A AU5345494A (en)	1992-10-05	1993-10-05	Pharmaceutical composition for site-specific release of a clot-dissolving protein
CA002146324A CA2146324A1 (en)	1992-10-05	1993-10-05	Pharmaceutical composition for the site-specific release of clot-dissolving protein and method for the preparation thereof
AT93923685T ATE171073T1 (de)	1992-10-05	1993-10-05	Pharmazeutische zusammensetzung für ortsspezifische abgabe von blutgerinselauflösende proteine
NO951219A NO951219L (no)	1992-10-05	1995-03-30	Farmasöytisk preparat til behandling av blodklumper og fremgangsmåte til fremstilling derav

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
NL9201722		1992-10-05
NL9201722A NL9201722A (nl)	1992-10-05	1992-10-05	Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan.

Publications (1)

Publication Number	Publication Date
NL9201722A true NL9201722A (nl)	1994-05-02

Family

ID=19861342

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NL9201722A NL9201722A (nl)	1992-10-05	1992-10-05	Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan.

Country Status (9)

Country	Link
EP (1)	EP0662841B1 (de)
JP (1)	JPH08502060A (de)
AT (1)	ATE171073T1 (de)
AU (1)	AU5345494A (de)
CA (1)	CA2146324A1 (de)
DE (1)	DE69321131D1 (de)
NL (1)	NL9201722A (de)
NO (1)	NO951219L (de)
WO (1)	WO1994007537A1 (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20030220233A1 (en)	1994-01-24	2003-11-27	Neorx Corporation	Radiolabeled annexins
US5968477A (en)	1994-01-24	1999-10-19	Neorx Corporation	Radiolabeled annexin conjugates with hexose and a chelator
DE19529223A1 (de) *	1995-08-09	1997-02-13	Boehringer Mannheim Gmbh	Verwendung von Plasminogenaktivatoren zum lokalen Knochenaufbau
JP7511916B2 (ja) *	2019-04-12	2024-07-08	ユージーエルケーサイエンスエービー	腎臓を再調整するための方法および装置
BR112021020423A2 (pt) *	2019-04-12	2021-12-14	Uglx Res Ab	Método e aparelho para recondicionar órgãos

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE831867A (fr) *	1975-07-29	1976-01-29		Association d'un activateur du plasminogene, d'une part, et du plasminogene lui-meme
JPS52102975A (en) *	1976-02-24	1977-08-29	Toyota Motor Corp	Hydraulic driving system
US4193983A (en) *	1978-05-16	1980-03-18	Syva Company	Labeled liposome particle compositions and immunoassays therewith
EP0227400B1 (de) *	1985-12-16	1991-12-04	Ethicon, Inc.	Hemmung von post-chirurgischer Adhäsionsbildung durch topische Verabreichung von Gewebeplasminogenaktivator
US5000960A (en) *	1987-03-13	1991-03-19	Micro-Pak, Inc.	Protein coupling to lipid vesicles
JP2764264B2 (ja) *	1987-10-01	1998-06-11	株式会社ミドリ十字	線溶活性増強剤
US5013556A (en) *	1989-10-20	1991-05-07	Liposome Technology, Inc.	Liposomes with enhanced circulation time

1992
- 1992-10-05 NL NL9201722A patent/NL9201722A/nl not_active Application Discontinuation
1993
- 1993-10-05 DE DE69321131T patent/DE69321131D1/de not_active Expired - Lifetime
- 1993-10-05 WO PCT/NL1993/000195 patent/WO1994007537A1/en not_active Ceased
- 1993-10-05 JP JP6508918A patent/JPH08502060A/ja active Pending
- 1993-10-05 EP EP93923685A patent/EP0662841B1/de not_active Expired - Lifetime
- 1993-10-05 AU AU53454/94A patent/AU5345494A/en not_active Abandoned
- 1993-10-05 AT AT93923685T patent/ATE171073T1/de active
- 1993-10-05 CA CA002146324A patent/CA2146324A1/en not_active Abandoned
1995
- 1995-03-30 NO NO951219A patent/NO951219L/no unknown

Also Published As

Publication number	Publication date
EP0662841A1 (de)	1995-07-19
CA2146324A1 (en)	1994-04-14
DE69321131D1 (de)	1998-10-22
AU5345494A (en)	1994-04-26
EP0662841B1 (de)	1998-09-16
NO951219D0 (no)	1995-03-30
ATE171073T1 (de)	1998-10-15
JPH08502060A (ja)	1996-03-05
WO1994007537A1 (en)	1994-04-14
NO951219L (no)	1995-06-06

Legal Events

Date	Code	Title	Description
1994-05-02	A1B	A search report has been drawn up
1995-06-01	BV	The patent application has lapsed

Publication	Publication Date	Title
Koudelka et al.	2016	Liposomal nanocarriers for plasminogen activators
US10357448B2 (en)	2019-07-23	Echogenic vehicle for clinical delivery of plasminogen activator and other fibrin-binding therapeutics to thrombi
AU725442B2 (en)	2000-10-12	A pharmaceutical preparation for treating blood coagulation disorders
US6930087B2 (en)	2005-08-16	Pharmaceutical composition comprising factor VIII and neutral liposomes
US20090047356A1 (en)	2009-02-19	Tissue factor compositions and methods
Heeremans et al.	1995	Thrombolytic treatment with tissue-type plasminogen activator (t-PA) containing liposomes in rabbits: a comparison with free t-PA
US12161698B2 (en)	2024-12-10	Synthetic platelets
Elbayoumi et al.	2008	Liposomes for targeted delivery of antithrombotic drugs
MXPA03008864A (es)	2004-12-06	Composicion de liposoma para el suministro intracelular mejorado en un agente terapeutico.
Moghimi et al.	1992	Opsonophagocytosis of liposomes by peritoneal macrophages and bone marrow reticuloendothelial cells
AU785103B2 (en)	2006-09-14	Stabilized liquid preparation of the protease which activates blood coagulation factor VII, or of its proenzyme
JPH026405A (ja)	1990-01-10	経肺薬物送達用組成物
JP2002515447A (ja)	2002-05-28	抑制されない血管内フィブリンクロット形成の予防および治療のための組成物および方法
Kim et al.	1998	Prolonged systemic delivery of streptokinase using liposome
Chiu et al.	2003	Targeting of antibody conjugated, phosphatidylserine-containing liposomes to vascular cell adhesion molecule 1 for controlled thrombogenesis
NL9201722A (nl)	1994-05-02	Farmaceutische samenstelling voor de plaatsgebonden afgifte van een stolsel oplossend eiwit en werkwijze voor de bereiding daarvan.
US5658588A (en)	1997-08-19	Fibrinogen-coated liposomes
US20030147944A1 (en)	2003-08-07	Lipid carrier compositions with protected surface reactive functions
WO2009067407A2 (en)	2009-05-28	Compositions of matrix metalloproteinase activating endopeptidases for reducing intraocular pressure, and methods of use thereof
US20250134969A1 (en)	2025-05-01	Biosynthetic hemostat and uses thereof
Gregory	2018	Liposome-Encapsulated Hemoglobin as an Artificial Oxygen Carrier
KR20240042134A (ko)	2024-04-01	A형 혈우병 치료용 변형된 콜로이드 입자
WO1994013323A1 (en)	1994-06-23	Method of inhibiting the clearance of liposomes from the circulation
Chiu	2003	Liposomes with selective and controllable surface reactivity: Applications for tumor specific thrombosis
WO2020061670A1 (pt)	2020-04-02	Formulação lipossomal, composição farmacêutica, uso de uma formulação lipossomal, método para tratamento de câncer, e, processo para preparação de uma formulação lipossomal