RU2668794C2 - Композиция, содержащая инкапсулированный антагомир - Google Patents
Композиция, содержащая инкапсулированный антагомир Download PDFInfo
- Publication number
- RU2668794C2 RU2668794C2 RU2015134770A RU2015134770A RU2668794C2 RU 2668794 C2 RU2668794 C2 RU 2668794C2 RU 2015134770 A RU2015134770 A RU 2015134770A RU 2015134770 A RU2015134770 A RU 2015134770A RU 2668794 C2 RU2668794 C2 RU 2668794C2
- Authority
- RU
- Russia
- Prior art keywords
- seq
- sequence
- mir
- nucleotide identity
- microspheres
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 51
- 239000004005 microsphere Substances 0.000 claims abstract description 157
- 239000003112 inhibitor Substances 0.000 claims abstract description 66
- 229920000642 polymer Polymers 0.000 claims abstract description 40
- 239000002243 precursor Substances 0.000 claims abstract description 40
- 206010000891 acute myocardial infarction Diseases 0.000 claims abstract description 35
- 230000033115 angiogenesis Effects 0.000 claims abstract description 29
- 208000033774 Ventricular Remodeling Diseases 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 19
- 230000001772 anti-angiogenic effect Effects 0.000 claims abstract description 3
- 230000001747 exhibiting effect Effects 0.000 claims abstract 2
- 125000003729 nucleotide group Chemical group 0.000 claims description 193
- 239000002773 nucleotide Substances 0.000 claims description 188
- 239000002679 microRNA Substances 0.000 claims description 158
- 108091070501 miRNA Proteins 0.000 claims description 152
- 108091034117 Oligonucleotide Proteins 0.000 claims description 54
- 108091034121 miR-92a stem-loop Proteins 0.000 claims description 36
- 108091041519 miR-92a-3 stem-loop Proteins 0.000 claims description 36
- 230000000295 complement effect Effects 0.000 claims description 30
- 239000000074 antisense oligonucleotide Substances 0.000 claims description 28
- 238000012230 antisense oligonucleotides Methods 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 28
- 239000002904 solvent Substances 0.000 claims description 24
- 108091091751 miR-17 stem-loop Proteins 0.000 claims description 23
- 108091069239 miR-17-2 stem-loop Proteins 0.000 claims description 23
- 208000010125 myocardial infarction Diseases 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 238000011282 treatment Methods 0.000 claims description 21
- 108091080309 miR-483 stem-loop Proteins 0.000 claims description 20
- 108091033331 miR-503 stem-loop Proteins 0.000 claims description 20
- 108091038507 miR-92b stem-loop Proteins 0.000 claims description 20
- 108091081014 miR-92b-1 stem-loop Proteins 0.000 claims description 20
- 108091032846 miR-92b-2 stem loop Proteins 0.000 claims description 20
- 229920001577 copolymer Polymers 0.000 claims description 18
- 108091049679 miR-20a stem-loop Proteins 0.000 claims description 18
- 108091025616 miR-92a-2 stem-loop Proteins 0.000 claims description 18
- 108091028159 miR-92a-1 stem-loop Proteins 0.000 claims description 17
- 108700011259 MicroRNAs Proteins 0.000 claims description 16
- 108091057645 miR-15 stem-loop Proteins 0.000 claims description 16
- 108091031326 miR-15b stem-loop Proteins 0.000 claims description 16
- 108091027943 miR-16 stem-loop Proteins 0.000 claims description 16
- 108091056204 miR-16-2 stem-loop Proteins 0.000 claims description 16
- 108091087148 miR-20 stem-loop Proteins 0.000 claims description 16
- 108091066984 miR-20-1 stem-loop Proteins 0.000 claims description 16
- 108091076199 miR-20-2 stem-loop Proteins 0.000 claims description 16
- 108091039792 miR-20b stem-loop Proteins 0.000 claims description 16
- 108091055878 miR-20b-1 stem-loop Proteins 0.000 claims description 16
- 108091027746 miR-20b-2 stem-loop Proteins 0.000 claims description 16
- 108091092825 miR-24 stem-loop Proteins 0.000 claims description 16
- 108091047483 miR-24-2 stem-loop Proteins 0.000 claims description 16
- 108091032978 miR-24-3 stem-loop Proteins 0.000 claims description 16
- 108091064025 miR-24-4 stem-loop Proteins 0.000 claims description 16
- 108091074487 miR-34 stem-loop Proteins 0.000 claims description 16
- 108091092493 miR-34-1 stem-loop Proteins 0.000 claims description 16
- 108091059780 miR-34-2 stem-loop Proteins 0.000 claims description 16
- 108091029119 miR-34a stem-loop Proteins 0.000 claims description 16
- 108091079013 miR-34b Proteins 0.000 claims description 16
- 108091084018 miR-34b stem-loop Proteins 0.000 claims description 16
- 108091063470 miR-34b-1 stem-loop Proteins 0.000 claims description 16
- 108091049916 miR-34b-2 stem-loop Proteins 0.000 claims description 16
- 108091057222 miR-34b-3 stem-loop Proteins 0.000 claims description 16
- 108091092639 miR-34b-4 stem-loop Proteins 0.000 claims description 16
- 108091090583 miR-34c stem-loop Proteins 0.000 claims description 16
- 108091082133 miR-34c-1 stem-loop Proteins 0.000 claims description 16
- 108091041286 miR-374 stem-loop Proteins 0.000 claims description 16
- 108091047175 miR-374a stem-loop Proteins 0.000 claims description 16
- 108091048101 miR-374b stem-loop Proteins 0.000 claims description 16
- 108091056144 miR-374c stem-loop Proteins 0.000 claims description 16
- 150000007523 nucleic acids Chemical class 0.000 claims description 16
- 108091074057 miR-16-1 stem-loop Proteins 0.000 claims description 15
- 108091048857 miR-24-1 stem-loop Proteins 0.000 claims description 15
- 239000012634 fragment Substances 0.000 claims description 12
- 108091059456 miR-92-1 stem-loop Proteins 0.000 claims description 12
- 108091084336 miR-92-2 stem-loop Proteins 0.000 claims description 12
- 108020004707 nucleic acids Proteins 0.000 claims description 12
- 102000039446 nucleic acids Human genes 0.000 claims description 12
- 238000007634 remodeling Methods 0.000 claims description 10
- 210000002216 heart Anatomy 0.000 claims description 9
- 238000012986 modification Methods 0.000 claims description 9
- 230000004048 modification Effects 0.000 claims description 9
- 108091093037 Peptide nucleic acid Proteins 0.000 claims description 8
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 6
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 claims description 6
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 6
- 229940124597 therapeutic agent Drugs 0.000 claims description 6
- 239000003708 ampul Substances 0.000 claims description 5
- 239000002299 complementary DNA Substances 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 230000000747 cardiac effect Effects 0.000 claims description 4
- 108091032955 Bacterial small RNA Proteins 0.000 claims description 3
- 108091028664 Ribonucleotide Proteins 0.000 claims description 3
- 239000005547 deoxyribonucleotide Substances 0.000 claims description 3
- 125000002637 deoxyribonucleotide group Chemical group 0.000 claims description 3
- 239000002336 ribonucleotide Substances 0.000 claims description 3
- 125000002652 ribonucleotide group Chemical group 0.000 claims description 3
- 230000037429 base substitution Effects 0.000 claims description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims 2
- 229960005181 morphine Drugs 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 26
- 229940122938 MicroRNA inhibitor Drugs 0.000 abstract description 15
- 239000000126 substance Substances 0.000 abstract description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 210000001519 tissue Anatomy 0.000 description 32
- 230000014509 gene expression Effects 0.000 description 29
- 239000000839 emulsion Substances 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000002347 injection Methods 0.000 description 22
- 239000007924 injection Substances 0.000 description 22
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 15
- 230000002107 myocardial effect Effects 0.000 description 14
- 206010061216 Infarction Diseases 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- 239000002245 particle Substances 0.000 description 13
- 239000008213 purified water Substances 0.000 description 13
- 230000002792 vascular Effects 0.000 description 13
- 241001465754 Metazoa Species 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 12
- 229940079593 drug Drugs 0.000 description 12
- 230000005764 inhibitory process Effects 0.000 description 12
- 238000002592 echocardiography Methods 0.000 description 11
- 238000001704 evaporation Methods 0.000 description 11
- 230000000302 ischemic effect Effects 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 108020004414 DNA Proteins 0.000 description 10
- 241000282887 Suidae Species 0.000 description 10
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 10
- 210000001367 artery Anatomy 0.000 description 10
- 230000017531 blood circulation Effects 0.000 description 10
- 210000004204 blood vessel Anatomy 0.000 description 10
- 230000007574 infarction Effects 0.000 description 10
- 238000001990 intravenous administration Methods 0.000 description 10
- 210000004165 myocardium Anatomy 0.000 description 9
- 230000008569 process Effects 0.000 description 9
- 241000282898 Sus scrofa Species 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000006378 damage Effects 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 7
- 230000002035 prolonged effect Effects 0.000 description 7
- 108090000623 proteins and genes Proteins 0.000 description 7
- 239000011780 sodium chloride Substances 0.000 description 7
- 102000006382 Ribonucleases Human genes 0.000 description 6
- 108010083644 Ribonucleases Proteins 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 230000008020 evaporation Effects 0.000 description 6
- 238000009396 hybridization Methods 0.000 description 6
- -1 methyleneimino Chemical group 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 208000012661 Dyskinesia Diseases 0.000 description 5
- 230000004071 biological effect Effects 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 210000004351 coronary vessel Anatomy 0.000 description 5
- 210000005240 left ventricle Anatomy 0.000 description 5
- 230000001338 necrotic effect Effects 0.000 description 5
- 210000000056 organ Anatomy 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 229940071643 prefilled syringe Drugs 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000010410 reperfusion Effects 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 238000013268 sustained release Methods 0.000 description 5
- 239000012730 sustained-release form Substances 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000002604 ultrasonography Methods 0.000 description 5
- ASJSAQIRZKANQN-CRCLSJGQSA-N 2-deoxy-D-ribose Chemical compound OC[C@@H](O)[C@@H](O)CC=O ASJSAQIRZKANQN-CRCLSJGQSA-N 0.000 description 4
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 108091028043 Nucleic acid sequence Proteins 0.000 description 4
- 239000004372 Polyvinyl alcohol Substances 0.000 description 4
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 4
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 4
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 4
- 206010003119 arrhythmia Diseases 0.000 description 4
- 229920000249 biocompatible polymer Polymers 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000004020 conductor Substances 0.000 description 4
- 238000009826 distribution Methods 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 238000011156 evaluation Methods 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000006698 induction Effects 0.000 description 4
- 108091007426 microRNA precursor Proteins 0.000 description 4
- 239000011859 microparticle Substances 0.000 description 4
- 239000000902 placebo Substances 0.000 description 4
- 229940068196 placebo Drugs 0.000 description 4
- 229920002451 polyvinyl alcohol Polymers 0.000 description 4
- 102000004169 proteins and genes Human genes 0.000 description 4
- 238000010839 reverse transcription Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- 239000003981 vehicle Substances 0.000 description 4
- 230000002861 ventricular Effects 0.000 description 4
- 102100027211 Albumin Human genes 0.000 description 3
- 108010088751 Albumins Proteins 0.000 description 3
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 3
- 108091030146 MiRBase Proteins 0.000 description 3
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000006793 arrhythmia Effects 0.000 description 3
- 230000010108 arterial embolization Effects 0.000 description 3
- 229920002988 biodegradable polymer Polymers 0.000 description 3
- 238000004422 calculation algorithm Methods 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000035876 healing Effects 0.000 description 3
- 230000000004 hemodynamic effect Effects 0.000 description 3
- 230000001771 impaired effect Effects 0.000 description 3
- 238000001802 infusion Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 230000004089 microcirculation Effects 0.000 description 3
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 108091007428 primary miRNA Proteins 0.000 description 3
- 230000000717 retained effect Effects 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- XBBVURRQGJPTHH-UHFFFAOYSA-N 2-hydroxyacetic acid;2-hydroxypropanoic acid Chemical compound OCC(O)=O.CC(O)C(O)=O XBBVURRQGJPTHH-UHFFFAOYSA-N 0.000 description 2
- 206010002329 Aneurysm Diseases 0.000 description 2
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 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 2
- 206010019280 Heart failures Diseases 0.000 description 2
- 206010020565 Hyperaemia Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 101710163270 Nuclease Proteins 0.000 description 2
- 238000002123 RNA extraction Methods 0.000 description 2
- 102000000574 RNA-Induced Silencing Complex Human genes 0.000 description 2
- 108010016790 RNA-Induced Silencing Complex Proteins 0.000 description 2
- 229960005305 adenosine Drugs 0.000 description 2
- 230000002491 angiogenic effect Effects 0.000 description 2
- 238000002399 angioplasty Methods 0.000 description 2
- 230000000692 anti-sense effect Effects 0.000 description 2
- 239000008346 aqueous phase Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 239000004621 biodegradable polymer Substances 0.000 description 2
- 230000031018 biological processes and functions Effects 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 210000004413 cardiac myocyte Anatomy 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 230000003828 downregulation Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000010102 embolization Effects 0.000 description 2
- 230000002255 enzymatic effect Effects 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 210000003191 femoral vein Anatomy 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 238000003780 insertion Methods 0.000 description 2
- 230000037431 insertion Effects 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000001361 intraarterial administration Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 208000028867 ischemia Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 238000002595 magnetic resonance imaging Methods 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000013081 microcrystal Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 108091027963 non-coding RNA Proteins 0.000 description 2
- 102000042567 non-coding RNA Human genes 0.000 description 2
- 239000002357 osmotic agent Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 230000001023 pro-angiogenic effect Effects 0.000 description 2
- 230000001536 pro-arrhythmogenic effect Effects 0.000 description 2
- 238000012545 processing Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 229920002477 rna polymer Polymers 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 210000003606 umbilical vein Anatomy 0.000 description 2
- 201000011531 vascular cancer Diseases 0.000 description 2
- 206010055031 vascular neoplasm Diseases 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- WROTXLSEMHAZEA-UHFFFAOYSA-N 4-diaminophosphoryloxymorpholine Chemical compound NP(N)(=O)ON1CCOCC1 WROTXLSEMHAZEA-UHFFFAOYSA-N 0.000 description 1
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 1
- 241000256182 Anopheles gambiae Species 0.000 description 1
- 241000256844 Apis mellifera Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 208000020446 Cardiac disease Diseases 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 241000251571 Ciona intestinalis Species 0.000 description 1
- 241000500138 Ciona savignyi Species 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 241000252212 Danio rerio Species 0.000 description 1
- 241000255601 Drosophila melanogaster Species 0.000 description 1
- 241000255313 Drosophila pseudoobscura Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091070489 Homo sapiens miR-17 stem-loop Proteins 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 241000282560 Macaca mulatta Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 241001482072 Oikopleura dioica Species 0.000 description 1
- 238000012408 PCR amplification Methods 0.000 description 1
- 206010057249 Phagocytosis Diseases 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 229920002732 Polyanhydride Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229920001213 Polysorbate 20 Polymers 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 102000014450 RNA Polymerase III Human genes 0.000 description 1
- 108010078067 RNA Polymerase III Proteins 0.000 description 1
- 229940076189 RNA modulator Drugs 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- 241000269457 Xenopus tropicalis Species 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000002877 alkyl aryl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000002344 aminooxy group Chemical group [H]N([H])O[*] 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000003126 arrythmogenic effect Effects 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 239000003124 biologic agent Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 208000006218 bradycardia Diseases 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 230000007681 cardiovascular toxicity Effects 0.000 description 1
- 239000004359 castor oil Substances 0.000 description 1
- 235000019438 castor oil Nutrition 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol group Chemical group [C@@H]1(CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C)[C@H](C)CCCC(C)C HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000004590 computer program Methods 0.000 description 1
- 230000009091 contractile dysfunction Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000007887 coronary angioplasty Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000002716 delivery method Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 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 1
- 201000010099 disease Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 230000000142 dyskinetic effect Effects 0.000 description 1
- 230000002497 edematous effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000020764 fibrinolysis Effects 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 230000030279 gene silencing Effects 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 210000002064 heart cell Anatomy 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 210000005003 heart tissue Anatomy 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000008105 immune reaction Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 230000003562 morphometric effect Effects 0.000 description 1
- 238000013425 morphometry Methods 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000000399 optical microscopy Methods 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- CWGKROHVCQJSPJ-UHFFFAOYSA-N oxathiasilirane Chemical compound O1[SiH2]S1 CWGKROHVCQJSPJ-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 210000003540 papillary muscle Anatomy 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 230000008782 phagocytosis Effects 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 238000013310 pig model Methods 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002463 poly(p-dioxanone) polymer Polymers 0.000 description 1
- 229920001281 polyalkylene Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920002721 polycyanoacrylate Polymers 0.000 description 1
- 239000000622 polydioxanone Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002959 polymer blend Polymers 0.000 description 1
- 229940051841 polyoxyethylene ether Drugs 0.000 description 1
- 229920000056 polyoxyethylene ether Polymers 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229940068977 polysorbate 20 Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- 238000003753 real-time PCR Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 230000014493 regulation of gene expression Effects 0.000 description 1
- 230000009711 regulatory function Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 238000004626 scanning electron microscopy Methods 0.000 description 1
- 230000036573 scar formation Effects 0.000 description 1
- 210000002186 septum of brain Anatomy 0.000 description 1
- 238000002864 sequence alignment Methods 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000012798 spherical particle Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-M sulfamate Chemical compound NS([O-])(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-M 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- MNRILEROXIRVNJ-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=NC=N[C]21 MNRILEROXIRVNJ-UHFFFAOYSA-N 0.000 description 1
- 229960003087 tioguanine Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 238000012285 ultrasound imaging Methods 0.000 description 1
- 230000004862 vasculogenesis Effects 0.000 description 1
Images
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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/10—Type of nucleic acid
- C12N2310/11—Antisense
- C12N2310/113—Antisense targeting other non-coding nucleic acids, e.g. antagomirs
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2310/00—Structure or type of the nucleic acid
- C12N2310/30—Chemical structure
- C12N2310/32—Chemical structure of the sugar
- C12N2310/323—Chemical structure of the sugar modified ring structure
- C12N2310/3231—Chemical structure of the sugar modified ring structure having an additional ring, e.g. LNA, ENA
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2320/00—Applications; Uses
- C12N2320/30—Special therapeutic applications
- C12N2320/32—Special delivery means, e.g. tissue-specific
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- General Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Microbiology (AREA)
- Physics & Mathematics (AREA)
- Biophysics (AREA)
- Plant Pathology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13305082.3A EP2759595B1 (en) | 2013-01-24 | 2013-01-24 | Composition comprising an encapsulated antagomir |
| EP13305082.3 | 2013-01-24 | ||
| PCT/IB2014/058500 WO2014115103A1 (en) | 2013-01-24 | 2014-01-23 | Composition comprising an encapsulated antagomir |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2015134770A RU2015134770A (ru) | 2017-03-03 |
| RU2668794C2 true RU2668794C2 (ru) | 2018-10-02 |
Family
ID=47683670
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015134770A RU2668794C2 (ru) | 2013-01-24 | 2014-01-23 | Композиция, содержащая инкапсулированный антагомир |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US20150352055A1 (enExample) |
| EP (2) | EP2759595B1 (enExample) |
| JP (1) | JP2016506923A (enExample) |
| KR (1) | KR20160018451A (enExample) |
| CN (1) | CN105229151A (enExample) |
| AU (1) | AU2014208419A1 (enExample) |
| BR (1) | BR112015017650A2 (enExample) |
| CA (1) | CA2898958A1 (enExample) |
| ES (2) | ES2606636T3 (enExample) |
| HK (1) | HK1219753A1 (enExample) |
| HU (1) | HUE032125T2 (enExample) |
| MX (1) | MX2015009323A (enExample) |
| PL (1) | PL2759595T3 (enExample) |
| RU (1) | RU2668794C2 (enExample) |
| WO (1) | WO2014115103A1 (enExample) |
| ZA (1) | ZA201505602B (enExample) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6208228B2 (ja) | 2012-06-21 | 2017-10-04 | ミラゲン セラピューティクス， インコーポレイテッド | ロックド核酸モチーフを含むオリゴヌクレオチドベースの阻害剤 |
| EP3247716A4 (en) * | 2015-01-20 | 2018-10-17 | Miragen Therapeutics, Inc. | Mir-92 inhibitors and uses thereof |
| WO2018183127A1 (en) * | 2017-03-25 | 2018-10-04 | MiRagen Therapeutics, Inc. | Mir-92 inhibitors for treatment of heart failure |
| CN113490488A (zh) * | 2019-03-14 | 2021-10-08 | M技术株式会社 | Plga微粒子、其缓释制剂以及其制造方法 |
| CN110484537B (zh) * | 2019-09-02 | 2021-07-27 | 中国水产科学研究院淡水渔业研究中心 | 一种miR-92促进剂及其注射剂的制备方法和应用 |
| CN110804659B (zh) * | 2019-10-23 | 2023-02-03 | 华南农业大学 | 一种血清外泌体ssc-miR-92b-3p作为母猪早期妊娠诊断分子标志物的应用 |
| CN110917359A (zh) * | 2019-11-21 | 2020-03-27 | 武汉理工大学 | 离子键自组装制备PEG-P（Asp-AP）-ANTAGOMIR-RNA微球 |
| WO2021251526A1 (ko) * | 2020-06-11 | 2021-12-16 | 주식회사 프로스테믹스 | 신규한 mirna 유사체 및 이의 용도 |
| CN111729088B (zh) * | 2020-08-21 | 2020-12-15 | 江苏申基生物科技有限公司 | 一种微小核糖核酸miR-34a偶联探针及其制备方法 |
| WO2025050037A1 (en) * | 2023-08-31 | 2025-03-06 | The Regents Of The University Of Colorado, A Body Corporate | Microrna-15b antagomir and cerium oxide nanoparticles, and uses of same for treatment of intrauterine growth restriction |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8383158B2 (en) * | 2003-04-15 | 2013-02-26 | Abbott Cardiovascular Systems Inc. | Methods and compositions to treat myocardial conditions |
| EP1648914A4 (en) * | 2003-07-31 | 2009-12-16 | Regulus Therapeutics Inc | OLIGOMERIC COMPOUNDS AND COMPOSITIONS USEFUL FOR MODULATING SMALL NON-CODING RNA |
| US8288356B2 (en) * | 2007-10-04 | 2012-10-16 | Santaris Pharma A/S | MicroRNAs |
| DE102007052114B4 (de) * | 2007-10-30 | 2011-01-05 | T2Cure Gmbh | Verfahren zur Modulation der Funktion, des Wachstums oder der Differenzierung einer Zelle |
| GB0814302D0 (en) * | 2008-08-05 | 2008-10-01 | Coretherapix Slu | Compounds and methods |
| CA2763156A1 (en) * | 2009-05-20 | 2010-11-25 | Board Of Regents, The University Of Texas System | Identification of micro-rnas involved in post-myocardial infarction remodeling and heart failure |
-
2013
- 2013-01-24 EP EP13305082.3A patent/EP2759595B1/en not_active Not-in-force
- 2013-01-24 ES ES13305082.3T patent/ES2606636T3/es active Active
- 2013-01-24 PL PL13305082T patent/PL2759595T3/pl unknown
- 2013-01-24 HU HUE13305082A patent/HUE032125T2/en unknown
-
2014
- 2014-01-23 AU AU2014208419A patent/AU2014208419A1/en not_active Abandoned
- 2014-01-23 CA CA2898958A patent/CA2898958A1/en not_active Abandoned
- 2014-01-23 RU RU2015134770A patent/RU2668794C2/ru not_active IP Right Cessation
- 2014-01-23 ES ES14706098.2T patent/ES2688160T3/es active Active
- 2014-01-23 EP EP14706098.2A patent/EP2948551B1/en not_active Not-in-force
- 2014-01-23 KR KR1020157022914A patent/KR20160018451A/ko not_active Withdrawn
- 2014-01-23 CN CN201480017728.3A patent/CN105229151A/zh active Pending
- 2014-01-23 HK HK16107653.5A patent/HK1219753A1/zh unknown
- 2014-01-23 WO PCT/IB2014/058500 patent/WO2014115103A1/en not_active Ceased
- 2014-01-23 MX MX2015009323A patent/MX2015009323A/es unknown
- 2014-01-23 BR BR112015017650A patent/BR112015017650A2/pt not_active IP Right Cessation
- 2014-01-23 US US14/763,181 patent/US20150352055A1/en not_active Abandoned
- 2014-01-23 JP JP2015554285A patent/JP2016506923A/ja active Pending
-
2015
- 2015-08-04 ZA ZA2015/05602A patent/ZA201505602B/en unknown
Non-Patent Citations (8)
| Title |
|---|
| BONAUER A. et al., MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice, Science, 2009, V. 324, N. 5935, p. 1710-1713. * |
| BONAUER A. et al., MicroRNA-92a controls angiogenesis and functional recovery of ischemic tissues in mice, Science, 2009, V. 324, N. 5935, p. 1710-1713. NAFEE N. at al., Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: effect of the formulation parameters on complexation and transfection of antisense oligonucleotides, Nanomedicine: Nanotechnology, Biology, and Medicine, 2007, V. 3, N. 3, p. 173-183. LUO G. et al., RNA interference of MBD1 in BxPC-3 human pancreatic cancer cells delivered by PLGA-poloxamer nanoparticles, Cancer biology and therapy, 2009, V. 8, N. 7, p. 594-598. D’ANGELO I. et al., Improved delivery of angiogenesis inhibitors from PLGA: poloxamer blend micro-and nanoparticles, Journal of microencapsulation, 2010, V. 27, N. 1, p. 57-66. CHENG C. et al., Polymer Nanoparticle-Mediated Delevery of MicroRNA Inhibition and Alternative Splicing, Molecular pharmaceutics, 2012, V. 9, N. 5, p. 1481-1488. JAIN R.A., The manufacturing techniques of various drug loaded biodeg * |
| CHENG C. et al., Polymer Nanoparticle-Mediated Delevery of MicroRNA Inhibition and Alternative Splicing, Molecular pharmaceutics, 2012, V. 9, N. 5, p. 1481-1488. * |
| D’ANGELO I. et al., Improved delivery of angiogenesis inhibitors from PLGA: poloxamer blend micro-and nanoparticles, Journal of microencapsulation, 2010, V. 27, N. 1, p. 57-66. * |
| JAIN R.A., The manufacturing techniques of various drug loaded biodegradable poly (lactide-co-glycolide)(PLGA) devices, Biomaterials, 2000, V. 21, N. 23, p.2475-2490. * |
| LUO G. et al., RNA interference of MBD1 in BxPC-3 human pancreatic cancer cells delivered by PLGA-poloxamer nanoparticles, Cancer biology and therapy, 2009, V. 8, N. 7, p. 594-598. * |
| NAFEE N. at al., Chitosan-coated PLGA nanoparticles for DNA/RNA delivery: effect of the formulation parameters on complexation and transfection of antisense oligonucleotides, Nanomedicine: Nanotechnology, Biology, and Medicine, 2007, V. 3, N. 3, p. 173-183. * |
| КОРОБОВ Г. А. и др., Ишемическая болезнь сердца: регулирование с помощью микроРНК, Кардиологический вестник, 2011, Т. 6, N. 2, с. 5-9. * |
Also Published As
| Publication number | Publication date |
|---|---|
| PL2759595T3 (pl) | 2017-09-29 |
| ES2606636T3 (es) | 2017-03-24 |
| KR20160018451A (ko) | 2016-02-17 |
| EP2948551A1 (en) | 2015-12-02 |
| MX2015009323A (es) | 2016-04-04 |
| CN105229151A (zh) | 2016-01-06 |
| BR112015017650A2 (pt) | 2017-11-21 |
| HK1219753A1 (zh) | 2017-04-13 |
| ZA201505602B (en) | 2017-05-31 |
| EP2759595A1 (en) | 2014-07-30 |
| WO2014115103A1 (en) | 2014-07-31 |
| US20150352055A1 (en) | 2015-12-10 |
| HUE032125T2 (en) | 2017-08-28 |
| JP2016506923A (ja) | 2016-03-07 |
| RU2015134770A (ru) | 2017-03-03 |
| EP2759595B1 (en) | 2016-09-14 |
| ES2688160T3 (es) | 2018-10-31 |
| AU2014208419A1 (en) | 2015-08-13 |
| EP2948551B1 (en) | 2018-05-02 |
| CA2898958A1 (en) | 2014-07-31 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2668794C2 (ru) | Композиция, содержащая инкапсулированный антагомир | |
| US9457046B2 (en) | Compounds for the treatment of ischemic injury | |
| AU2017200853B2 (en) | MiRNA and its diagnostic therapeutic uses in diseases or conditions associated with melanoma, or in diseases or conditions associated with activated BRAF pathway | |
| US12234455B2 (en) | Therapeutic oligonucleotides | |
| JP2015525081A5 (enExample) | ||
| EP3329004B1 (en) | Therapeutic oligonucleotides | |
| EP4634386A1 (en) | Antisense oligonucleotide analogs of mir-29 and uses thereof | |
| JPWO2015133637A1 (ja) | マイクロｒｎａ封入ナノ粒子及びその医薬用途 | |
| CN120584186A (zh) | 用于在静脉血栓栓塞的治疗中使用的药物组合物 | |
| WO2022251322A1 (en) | Methods of using mir-3075-5p to improve insulin sensitivity and compositions therefor | |
| BR122024021791A2 (pt) | Oligonucleotídeo para uso no tratamento e/ou prevenção de uma doença que compreende o alongamento alternativo dos telômeros, oligonucleotídeo para uso no tratamento e/ou prevenção de uma condição não cancerosa associada à disfunção do telômero e composição farmacêutica | |
| BR112018001782B1 (pt) | Oligonucleotídeo para uso no tratamento e/ou prevenção de uma doença que compreende o alongamento alternativo dos telômeros, oligonucleotídeo para uso no tratamento e/ou prevenção de uma condição não cancerosa associada à disfunção do telômero e composição farmacêutica | |
| KR20190134753A (ko) | 골 손실 및 근육 기능 감소와 관련된 병리학적 상태를 치료하는데 이용하기 위한 마이크로rna 19a/19b |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | The patent is invalid due to non-payment of fees |
Effective date: 20200124 |