JP7454757B2 - 放射線不透過性ポリマーを含む液体塞栓組成物 - Google Patents
放射線不透過性ポリマーを含む液体塞栓組成物 Download PDFInfo
- Publication number
- JP7454757B2 JP7454757B2 JP2022100570A JP2022100570A JP7454757B2 JP 7454757 B2 JP7454757 B2 JP 7454757B2 JP 2022100570 A JP2022100570 A JP 2022100570A JP 2022100570 A JP2022100570 A JP 2022100570A JP 7454757 B2 JP7454757 B2 JP 7454757B2
- Authority
- JP
- Japan
- Prior art keywords
- polymer
- liquid embolic
- embolic composition
- composition according
- liquid
- 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.)
- Active
Links
- 229920000642 polymer Polymers 0.000 title claims description 72
- 239000007788 liquid Substances 0.000 title claims description 58
- 239000000203 mixture Substances 0.000 title claims description 52
- 230000003073 embolic effect Effects 0.000 title claims description 41
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 28
- 239000002244 precipitate Substances 0.000 claims description 24
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 20
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 17
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 12
- 239000003960 organic solvent Substances 0.000 claims description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- 229910052740 iodine Inorganic materials 0.000 claims description 8
- 239000011630 iodine Substances 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- -1 oxolan-2-ylmethoxy Chemical group 0.000 claims description 6
- 125000005647 linker group Chemical group 0.000 claims description 5
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- CYSGHNMQYZDMIA-UHFFFAOYSA-N 1,3-Dimethyl-2-imidazolidinon Chemical compound CN1CCN(C)C1=O CYSGHNMQYZDMIA-UHFFFAOYSA-N 0.000 claims description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 229920001577 copolymer Polymers 0.000 claims description 3
- GUVUOGQBMYCBQP-UHFFFAOYSA-N dmpu Chemical compound CN1CCCN(C)C1=O GUVUOGQBMYCBQP-UHFFFAOYSA-N 0.000 claims description 3
- 229920001519 homopolymer Polymers 0.000 claims description 3
- 229940116333 ethyl lactate Drugs 0.000 claims description 2
- 125000005702 oxyalkylene group Chemical group 0.000 claims description 2
- 239000003880 polar aprotic solvent Substances 0.000 claims description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 2
- 238000013162 therapeutic embolization Methods 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical group OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 claims 1
- 229940126585 therapeutic drug Drugs 0.000 claims 1
- 235000013675 iodine Nutrition 0.000 description 16
- 238000009472 formulation Methods 0.000 description 15
- 208000005189 Embolism Diseases 0.000 description 11
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 230000010102 embolization Effects 0.000 description 9
- 238000001556 precipitation Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 239000013543 active substance Substances 0.000 description 6
- 239000002245 particle Substances 0.000 description 6
- ZMZGFLUUZLELNE-UHFFFAOYSA-N 2,3,5-triiodobenzoic acid Chemical compound OC(=O)C1=CC(I)=CC(I)=C1I ZMZGFLUUZLELNE-UHFFFAOYSA-N 0.000 description 5
- XMTQQYYKAHVGBJ-UHFFFAOYSA-N 3-(3,4-DICHLOROPHENYL)-1,1-DIMETHYLUREA Chemical compound CN(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XMTQQYYKAHVGBJ-UHFFFAOYSA-N 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 239000005293 duran Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 230000015271 coagulation Effects 0.000 description 4
- 238000005345 coagulation Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000008021 deposition Effects 0.000 description 3
- 238000011049 filling Methods 0.000 description 3
- 238000011065 in-situ storage Methods 0.000 description 3
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 238000010603 microCT Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- CTPDSKVQLSDPLC-UHFFFAOYSA-N 2-(oxolan-2-ylmethoxy)ethanol Chemical compound OCCOCC1CCCO1 CTPDSKVQLSDPLC-UHFFFAOYSA-N 0.000 description 2
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 2
- 206010053567 Coagulopathies Diseases 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 2
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 2
- 206010046798 Uterine leiomyoma Diseases 0.000 description 2
- 125000006295 amino methylene group Chemical group [H]N(*)C([H])([H])* 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 230000005744 arteriovenous malformation Effects 0.000 description 2
- 230000017531 blood circulation Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 239000007810 chemical reaction solvent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000035602 clotting Effects 0.000 description 2
- 229940127089 cytotoxic agent Drugs 0.000 description 2
- 150000002009 diols Chemical group 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 238000013467 fragmentation Methods 0.000 description 2
- 238000006062 fragmentation reaction Methods 0.000 description 2
- 208000030304 gastrointestinal bleeding Diseases 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 201000010260 leiomyoma Diseases 0.000 description 2
- 239000004005 microsphere Substances 0.000 description 2
- 239000013618 particulate matter Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 230000005855 radiation Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000013049 sediment Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- WFKWXMTUELFFGS-UHFFFAOYSA-N tungsten Chemical compound [W] WFKWXMTUELFFGS-UHFFFAOYSA-N 0.000 description 2
- 229910052721 tungsten Inorganic materials 0.000 description 2
- 239000010937 tungsten Substances 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- 150000000185 1,3-diols Chemical group 0.000 description 1
- ROJLASMOZHOOOX-UHFFFAOYSA-N 2,3,5-triiodobenzaldehyde Chemical compound IC1=CC(I)=C(I)C(C=O)=C1 ROJLASMOZHOOOX-UHFFFAOYSA-N 0.000 description 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 206010002329 Aneurysm Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical group C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 1
- 229920000219 Ethylene vinyl alcohol Polymers 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- 230000021736 acetylation Effects 0.000 description 1
- 238000006640 acetylation reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000011543 agarose gel Substances 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- 229940045799 anthracyclines and related substance Drugs 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229960004562 carboplatin Drugs 0.000 description 1
- 190000008236 carboplatin Chemical compound 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229960005395 cetuximab Drugs 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 208000012839 conversion disease Diseases 0.000 description 1
- LRCTTYSATZVTRI-UHFFFAOYSA-L cyclohexane-1,2-diamine;platinum(4+);tetradecanoate Chemical compound [Pt+4].NC1CCCCC1N.CCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCC([O-])=O LRCTTYSATZVTRI-UHFFFAOYSA-L 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 238000011038 discontinuous diafiltration by volume reduction Methods 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 229960004679 doxorubicin Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229960001904 epirubicin Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 239000004715 ethylene vinyl alcohol Substances 0.000 description 1
- ZVYVPGLRVWUPMP-FYSMJZIKSA-N exatecan Chemical compound C1C[C@H](N)C2=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC3=CC(F)=C(C)C1=C32 ZVYVPGLRVWUPMP-FYSMJZIKSA-N 0.000 description 1
- 229950009429 exatecan Drugs 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 238000001879 gelation Methods 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
- RZXDTJIXPSCHCI-UHFFFAOYSA-N hexa-1,5-diene-2,5-diol Chemical compound OC(=C)CCC(O)=C RZXDTJIXPSCHCI-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000002390 hyperplastic effect Effects 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 238000002324 minimally invasive surgery Methods 0.000 description 1
- 229950004962 miriplatin Drugs 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960003301 nivolumab Drugs 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 229960001756 oxaliplatin Drugs 0.000 description 1
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical class [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 1
- 229960000303 topotecan Drugs 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 229920006163 vinyl copolymer Polymers 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 210000000707 wrist Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0442—Polymeric X-ray contrast-enhancing agent comprising a halogenated group
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F12/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F12/02—Monomers containing only one unsaturated aliphatic radical
- C08F12/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F12/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by hetero atoms or groups containing heteroatoms
- C08F12/16—Halogens
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
- A61B17/12181—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B17/00—Surgical instruments, devices or methods, e.g. tourniquets
- A61B17/12—Surgical instruments, devices or methods, e.g. tourniquets for ligaturing or otherwise compressing tubular parts of the body, e.g. blood vessels, umbilical cord
- A61B17/12022—Occluding by internal devices, e.g. balloons or releasable wires
- A61B17/12131—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device
- A61B17/12181—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices
- A61B17/12186—Occluding by internal devices, e.g. balloons or releasable wires characterised by the type of occluding device formed by fluidized, gelatinous or cellular remodelable materials, e.g. embolic liquids, foams or extracellular matrices liquid materials adapted to be injected
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0447—Physical forms of mixtures of two different X-ray contrast-enhancing agents, containing at least one X-ray contrast-enhancing agent which is a halogenated organic compound
- A61K49/0452—Solutions, e.g. for injection
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F112/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F112/02—Monomers containing only one unsaturated aliphatic radical
- C08F112/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F112/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by hetero atoms or groups containing heteroatoms
- C08F112/16—Halogens
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F112/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F112/02—Monomers containing only one unsaturated aliphatic radical
- C08F112/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F112/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by hetero atoms or groups containing heteroatoms
- C08F112/22—Oxygen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F116/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical
- C08F116/02—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical by an alcohol radical
- C08F116/04—Acyclic compounds
- C08F116/06—Polyvinyl alcohol ; Vinyl alcohol
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F12/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F12/02—Monomers containing only one unsaturated aliphatic radical
- C08F12/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F12/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by hetero atoms or groups containing heteroatoms
- C08F12/22—Oxygen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/02—Monomers containing only one unsaturated aliphatic radical
- C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F212/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by heteroatoms or groups containing heteroatoms
- C08F212/16—Halogens
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F212/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an aromatic carbocyclic ring
- C08F212/02—Monomers containing only one unsaturated aliphatic radical
- C08F212/04—Monomers containing only one unsaturated aliphatic radical containing one ring
- C08F212/14—Monomers containing only one unsaturated aliphatic radical containing one ring substituted by heteroatoms or groups containing heteroatoms
- C08F212/22—Oxygen
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/28—Condensation with aldehydes or ketones
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/48—Isomerisation; Cyclisation
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F116/00—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical
- C08F116/38—Homopolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical by a acetal or ketal radical
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F16/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical
- C08F16/02—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical by an alcohol radical
- C08F16/04—Acyclic compounds
- C08F16/06—Polyvinyl alcohol ; Vinyl alcohol
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F16/00—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical
- C08F16/38—Homopolymers and copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical by an acetal or ketal radical
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F216/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical
- C08F216/02—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical by an alcohol radical
- C08F216/04—Acyclic compounds
- C08F216/06—Polyvinyl alcohol ; Vinyl alcohol
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F216/00—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical
- C08F216/38—Copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and at least one being terminated by an alcohol, ether, aldehydo, ketonic, acetal or ketal radical by an acetal or ketal radical
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Surgery (AREA)
- Epidemiology (AREA)
- Emergency Medicine (AREA)
- Medical Informatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Vascular Medicine (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Reproductive Health (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Materials For Medical Uses (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Description
第1の態様では、本発明は、式Iのペンダント基を有するポリマーを含有する液体組成物を提供する。
ポリマーは、好ましくは非架橋である。
天然のPVAポリマーは、アセチル化されていてもされていなくてもよく、一般に、天然のPVAのアセチル化のレベルは、50%から100%、好ましくは80%から100%の間である。
一実施形態では、ポリマーは、式1の複数の種類のペンダント基を含み、ポリマーはそれぞれ、nの値について互いに異なる。例えば、異なるnの値を有する2,3,4つ、又はそれ以上のペンダント基が存在し得る。
好ましい一実施形態では、水性溶媒は、薬学的に許容される緩衝液を含む。そのような緩衝液の例には、リン酸塩、クエン酸塩、トロメタミン及び酢酸塩が含まれる。
例示的な化学療法剤には、限定ではないがドキソルビシン、ダウナルビシン、エピルビシン、及びイダルビシンなどのアントラサイクリン系、限定ではないがイリノテカン、トポテカン、エキサテカンなどのカンプトテシン系、シスプラチン、オキサリプラチン、カルボプラチン、ミリプラチンなどのプラチン系、マイトマイシンC、5-フルオロウラシルなどの代謝抵抗物質、限定ではないがソラフェニブ、スニチニブ、レゴラフェニブ、ブリビンブ、ダセタニブ、ボスチニブ、エルロチニブ、ゲフィチニブ、イマチニブ及びバンデチニブ、ラパマイシン又はそれらの任意の組み合わせなどのマルチチロシンキナーゼ阻害剤が含まれる。
さらなる実施形態において、本発明は、医学的治療方法で使用するための本明細書に記載の薬学的活性成分を提供し、治療は、本明細書に記載の活性物質を含有する塞栓組成物の形態で医薬活性物質を患者に送達することを含み、そこから活性物質が治療中に溶出される。
実施例1:一般的な液体塞栓合成条件
窒素ブランケット下で予備乾燥した反応器に、PVA(通常、5~10g)、無水溶媒(通常、DMSO又はNMP、PVA質量に対して40体積量)、及び触媒(PVA質量に対して通常2.2体積量)を加えた。次に、攪拌した懸濁液を高温(約90℃)に加熱してPVAを溶解した。均一な溶液が得られたら混合物を所望の反応温度(通常50~80℃)に冷却した。2,3,5トリヨードベンズアルデヒド(TIBA-通常PVAジオール官能基に対して0.1~0.6当量)を加えた。反応物を窒素ブランケットの下で撹拌し、反応の変換を、TIBAの消費について高速液体クロマトグラフィー(HPLC)によってモニターした。所定時間(通常、化学基質の消費が停止したとき)に、逆溶媒(通常、アセトン、ジクロロメタン(DCM)、アセトニトリル(MeCN)、又はメチルtert-ブチルエーテル(TBME)、約40体積量)を滴下漏斗から滴下して加えた。上澄み液をフィルター膜を通して吸引して除去し、さらに反応溶媒(通常、40体積量)を加えて、固体が完全に溶解するまで撹拌した。この溶媒洗浄工程を最大3回繰り返した。次に、固体を反応溶媒に再溶解して水をゆっくりと加えることによって沈殿させた(通常、最大100体積量)。得られた凝集固体を上澄みから除去して、ブレンダー内において水(約1リットル)中で均質化した。懸濁液を濾過し、水(通常、100体積量)に再懸濁し、最大30分間懸濁して濾過した。中性pHが得られるまで水懸濁を繰り返し、次に湿った固体をアセトンに懸濁して(100体積量、30分間撹拌、2回繰り返し)、濾過して、30℃の高真空オーブンで最大24時間乾燥させた。表1は、液体塞栓製剤のヨウ素含有量を示す。
*=80%加水分解される。
**=88%加水分解される。
実施例2:ヨウ素化PVA液体塞栓プロトタイプの処方
プロトタイプ製剤は、以下のように調製した。実施例1に従って調製したヨウ素化PVAを10mlのバイアルに量り取り、全量が10ml未満で全体の濃度が4~20%(w/w)の範囲になるように目的の溶媒(通常はDMSO又はNMP)をバイアルに加えた。次に、懸濁液を含むバイアルを密封して超音波処理器に入れ、完全に溶解するまで(通常、約4時間)超音波処理した。表2は、液体塞栓製剤の例を示す。
液体サンプルからの溶媒(DMSO)の溶出を凝固の進行の尺度として用いた。テストは、UV分光光度計に接続したSotaxUSPII溶解浴で実施した。溶解浴を37.5℃に設定して、各容器を50rpmで撹拌しながら500mLのリン酸緩衝生理食塩水(PBS)で満たした。
表2a:低分子量製剤の沈殿時間
実施例4:沈殿充填体積
沈殿充填体積は、サンプルがPBS内で沈殿した後の液体塞栓サンプルの体積の減少率の測定値、及び、既知の液体体積からどのくらいの固体沈殿物が生成されるかについての測定値を提供する。
表3
粒子の生成は、液体塞栓性沈殿物の凝集性と安定性の尺度である。
針のない注射器を使用して、0.5mLの液体塞栓製剤を50mLのデュランボトル内の30±5mlのPBSに滴下して沈着させた。シリンジは、PBSの表面から12cmの高さに配置した。液体塞栓を10分間固化した。
表4
透明な取り外し可能なチューブをフローシステムに取り付け、取り外し可能なチューブを通してPBSを蠕動ポンプを使用して送り、血流状態を模倣した。2.4フレンチ(Fr)カテーテルを使用して、液体塞栓製剤を取り外し可能なチューブに送った。液体塞栓がカテーテルを離れてPBSと接触すると、取り外し可能なチューブ内に沈殿した。次に、沈殿物の長さをカテーテル先端の端から測定した。流量と速度の低下も記録した。「最長の前進」を記録した。逆流が生じた場合、その長さは「逆流の最長の長さ」(cm)としても記録した。カテーテルを沈殿試験装置のチューブから取り外して、取り外しの容易さを記録した。
表5
材料の放射線不透過性測定値を得るために、実施例6からの沈殿した製剤の1cmの切片を切り取り、温かい1%アガロースゲル(シグマアルドリッチ社製品コードA9539で調製)に包埋した。サンプルは、Nuncクライオチューブバイアル(シグマアルドリッチ社製品コードV7634、48mmx12.5mm)で調製し、タングステンアノードに適合する、英国バークシャーのRSSLラボラトリーズのBruker Skyscan 1172 Micro-CTスキャナーを使用してMicro-CTを使用してスキャンした。各サンプルは、64kVの電圧と155μAの電流とで動作するタングステンアノードを備えた同一の機器構成を使用して分析した。アルミフィルター(500μm)を使用した。
表6
interest)を作成した。次に画像をセグメント化してボイド構造からポリマーを分離した。次に、同日に取得した水標準を使用して、HUの放射線密度を計算した。
Claims (18)
- 有機溶媒中の溶液状態にある、式1のペンダント基を有するポリマーであって、
前記式1中、Xは結合、1~8個の炭素を有する連結基、又は、1~8個の炭素とO、N、及びSのうちの少なくとも1つから選択される1~4個のヘテロ原子とを有する連結基であり、nは1~4である前記ポリマーと、
治療薬と、
を含み、前記ポリマーは、20℃で通常の生理食塩水と接触すると沈殿するものである、治療用塞栓術に適した液体塞栓組成物。 - 前記有機溶媒は水混和性溶媒である、請求項1に記載の液体塞栓組成物。
- 前記nは1~3である、請求項1又は2に記載の液体塞栓組成物。
- 前記ポリマーは、式2a~2d
から選択されるペンダント基を含む、請求項1~3のいずれか一項に記載の液体塞栓組成物。 - 前記Xは結合、(C1-4)アルキレン、(C1-4)オキシアルキレン、及びアミノ(C1-4)アルキレンから選択される、請求項1~4のいずれか一項に記載の液体塞栓組成物。
- 前記Xは結合である、請求項1~5のいずれか一項に記載の液体塞栓組成物。
- 前記式1のペンダント基は、式3
のペンダント基である、請求項1~6のいずれか一項に記載の液体塞栓組成物。 - 前記ポリマーは、ビニルアルコール及びそのコポリマーから選択される、請求項1~7のいずれか一項に記載の液体塞栓組成物。
- 前記ポリマーは、ポリビニルアルコールホモポリマー又はコポリマーである、請求項8に記載の液体塞栓組成物。
- 前記nは2又は3である、請求項1~9のいずれか一項に記載の液体塞栓組成物。
- 前記ポリマーは非架橋である、請求項1~10のいずれか一項に記載の液体塞栓組成物。
- 前記ポリマーは生分解性である、請求項1~11のいずれか一項に記載の液体塞栓組成物。
- 前記ポリマーは非生分解性である、請求項1~11のいずれか一項に記載の液体塞栓組成物。
- 前記ポリマーは、乾燥ポリマーの10重量%(wt/wt)以上のヨウ素を含む、請求項1~13のいずれか一項に記載の液体塞栓組成物。
- 前記有機溶媒に溶解した3~70重量%(wt/wt)のポリマーを含む、請求項1~14のいずれか一項に記載の液体塞栓組成物。
- 前記ポリマーの沈殿物は少なくとも1000HUの放射線密度を有する請求項1~15のいずれか一項に記載の液体塞栓組成物。
- 前記有機溶媒は、極性非プロトン性溶媒である、請求項1~16のいずれか一項に記載の液体塞栓組成物。
- 前記有機溶媒は、ジメチルスルホキシド、ジメチルホルムアミド、N、N’-ジメチルプロピレン尿素、1,3-ジメチル-2-イミダゾリジノン、グリセロール、乳酸エチル、N-メチル-2-ピロリドン、及び、2-(オキソラン-2-イルメトキシ)エタノールから選択される、請求項1~17のいずれか一項に記載の液体塞栓組成物。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB1810784.7A GB201810784D0 (en) | 2018-06-29 | 2018-06-29 | Radiopaque polymers |
GB1810784.7 | 2018-06-29 | ||
JP2020561029A JP7095112B2 (ja) | 2018-06-29 | 2019-06-26 | 放射線不透過性ポリマー |
PCT/IB2019/055394 WO2020003153A1 (en) | 2018-06-29 | 2019-06-26 | Radiopaque polymers |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020561029A Division JP7095112B2 (ja) | 2018-06-29 | 2019-06-26 | 放射線不透過性ポリマー |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2022118197A JP2022118197A (ja) | 2022-08-12 |
JP7454757B2 true JP7454757B2 (ja) | 2024-03-25 |
Family
ID=63143523
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020561029A Active JP7095112B2 (ja) | 2018-06-29 | 2019-06-26 | 放射線不透過性ポリマー |
JP2022100570A Active JP7454757B2 (ja) | 2018-06-29 | 2022-06-22 | 放射線不透過性ポリマーを含む液体塞栓組成物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020561029A Active JP7095112B2 (ja) | 2018-06-29 | 2019-06-26 | 放射線不透過性ポリマー |
Country Status (9)
Country | Link |
---|---|
US (1) | US20210221928A1 (ja) |
EP (1) | EP3813886A1 (ja) |
JP (2) | JP7095112B2 (ja) |
CN (1) | CN112351798A (ja) |
AU (2) | AU2019293397B2 (ja) |
CA (1) | CA3096334C (ja) |
GB (1) | GB201810784D0 (ja) |
TW (1) | TW202000715A (ja) |
WO (1) | WO2020003153A1 (ja) |
Families Citing this family (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101744347B1 (ko) * | 2015-12-15 | 2017-06-08 | 한전원자력연료 주식회사 | 자체정렬구조를 가지는 상단고정체 |
KR101746780B1 (ko) * | 2015-12-15 | 2017-06-14 | 한전원자력연료 주식회사 | 수평회전구조를 가지는 상단고정체 |
GB201810784D0 (en) * | 2018-06-29 | 2018-08-15 | Biocompatibles Uk Ltd | Radiopaque polymers |
US20220242817A1 (en) | 2021-01-12 | 2022-08-04 | Boston Scientific Scimed Inc. | Iodinated compounds having radiocontrast properties |
CN117915963A (zh) | 2021-07-12 | 2024-04-19 | 波士顿科学国际有限公司 | 不透射线组合物 |
CN114262279B (zh) * | 2021-12-30 | 2022-12-16 | 上海汇禾医疗科技有限公司 | 一种x射线可显影分子、栓塞微球及其制备方法 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016529055A (ja) | 2013-09-06 | 2016-09-23 | バイオコンパティブルズ ユーケー リミテッド | 撮像可能なポリマー |
JP2016531921A (ja) | 2013-09-06 | 2016-10-13 | バイオコンパティブルズ ユーケー リミテッド | 放射線不透過性ポリマー |
JP7095112B2 (ja) | 2018-06-29 | 2022-07-04 | バイオコンパティブルズ ユーケー リミテッド | 放射線不透過性ポリマー |
Family Cites Families (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1263803B1 (en) * | 2000-03-13 | 2007-09-19 | BioCure, Inc. | Embolic compositions |
CN101513542B (zh) * | 2009-03-27 | 2012-08-15 | 山东大正医疗器械股份有限公司 | 一种含碘可长期自身显影液体栓塞剂的制备方法 |
EP2365009A1 (en) * | 2010-03-10 | 2011-09-14 | Universite Claude Bernard Lyon 1 (UCBL) | Radiopaque, non-biodegradable, water-insoluble iodinated benzyl ethers of poly(vinyl alcohol), preparation method thereof, injectable embolizing compositions containing thereof and use thereof |
-
2018
- 2018-06-29 GB GBGB1810784.7A patent/GB201810784D0/en not_active Ceased
-
2019
- 2019-06-26 AU AU2019293397A patent/AU2019293397B2/en active Active
- 2019-06-26 CN CN201980039152.3A patent/CN112351798A/zh active Pending
- 2019-06-26 US US17/252,564 patent/US20210221928A1/en active Pending
- 2019-06-26 WO PCT/IB2019/055394 patent/WO2020003153A1/en unknown
- 2019-06-26 TW TW108122411A patent/TW202000715A/zh unknown
- 2019-06-26 CA CA3096334A patent/CA3096334C/en active Active
- 2019-06-26 EP EP19765551.7A patent/EP3813886A1/en active Pending
- 2019-06-26 JP JP2020561029A patent/JP7095112B2/ja active Active
-
2022
- 2022-06-22 JP JP2022100570A patent/JP7454757B2/ja active Active
-
2023
- 2023-05-30 AU AU2023203353A patent/AU2023203353B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2016529055A (ja) | 2013-09-06 | 2016-09-23 | バイオコンパティブルズ ユーケー リミテッド | 撮像可能なポリマー |
JP2016531921A (ja) | 2013-09-06 | 2016-10-13 | バイオコンパティブルズ ユーケー リミテッド | 放射線不透過性ポリマー |
JP7095112B2 (ja) | 2018-06-29 | 2022-07-04 | バイオコンパティブルズ ユーケー リミテッド | 放射線不透過性ポリマー |
Also Published As
Publication number | Publication date |
---|---|
AU2023203353A1 (en) | 2023-06-29 |
CA3096334A1 (en) | 2020-01-02 |
AU2019293397A1 (en) | 2020-11-12 |
TW202000715A (zh) | 2020-01-01 |
CA3096334C (en) | 2023-09-26 |
AU2023203353B2 (en) | 2024-05-30 |
JP7095112B2 (ja) | 2022-07-04 |
EP3813886A1 (en) | 2021-05-05 |
AU2019293397B2 (en) | 2023-03-02 |
WO2020003153A1 (en) | 2020-01-02 |
JP2021520440A (ja) | 2021-08-19 |
CN112351798A (zh) | 2021-02-09 |
JP2022118197A (ja) | 2022-08-12 |
US20210221928A1 (en) | 2021-07-22 |
GB201810784D0 (en) | 2018-08-15 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP7454757B2 (ja) | 放射線不透過性ポリマーを含む液体塞栓組成物 | |
JP6983930B2 (ja) | 結像可能な塞栓性微小球 | |
JP5696165B2 (ja) | 放射線不透過性、非生分解性、水不溶性の、ポリ(ビニルアルコール)のヨウ素化ベンジルエーテル、その製造方法、それを含む注射可能な塞栓組成物、およびその使用方法 | |
JP7322073B2 (ja) | 放射線不透過性ポリマー | |
JP2003500114A (ja) | 新規の高粘度塞栓形成組成物 | |
US20230355833A1 (en) | Radiopaque polymers | |
WO2021069528A1 (fr) | Microsphere d'embolisation non degradable radio-opaque | |
JP2022046815A (ja) | 粒子を含むエマルジョン | |
WO2021069527A1 (fr) | Microsphere d'embolisation non degradable | |
CN117582535B (zh) | 一种液体栓塞剂及其制备方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220721 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20220721 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20230725 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20230801 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20231030 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20231121 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20231221 |
|
A711 | Notification of change in applicant |
Free format text: JAPANESE INTERMEDIATE CODE: A711 Effective date: 20240208 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 7454757 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |