JP2011526619A - 局所ドラッグデリバリーシステム、その方法、および、その組成物 - Google Patents
局所ドラッグデリバリーシステム、その方法、および、その組成物 Download PDFInfo
- Publication number
- JP2011526619A JP2011526619A JP2011515712A JP2011515712A JP2011526619A JP 2011526619 A JP2011526619 A JP 2011526619A JP 2011515712 A JP2011515712 A JP 2011515712A JP 2011515712 A JP2011515712 A JP 2011515712A JP 2011526619 A JP2011526619 A JP 2011526619A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- drug
- loader
- drugs
- polymer
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 129
- 239000000203 mixture Substances 0.000 title claims description 83
- 238000012377 drug delivery Methods 0.000 title description 11
- 230000000699 topical effect Effects 0.000 title description 2
- 239000003814 drug Substances 0.000 claims abstract description 231
- 229940079593 drug Drugs 0.000 claims abstract description 210
- 239000004055 small Interfering RNA Substances 0.000 claims abstract description 165
- 229920000642 polymer Polymers 0.000 claims abstract description 80
- 239000007943 implant Substances 0.000 claims abstract description 62
- 238000011282 treatment Methods 0.000 claims abstract description 53
- 108091032973 (ribonucleotides)n+m Proteins 0.000 claims abstract description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 claims abstract description 21
- 201000010099 disease Diseases 0.000 claims abstract description 21
- 230000009368 gene silencing by RNA Effects 0.000 claims abstract description 21
- 229920000307 polymer substrate Polymers 0.000 claims abstract description 15
- 108091027967 Small hairpin RNA Proteins 0.000 claims abstract description 14
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 5
- 206010061218 Inflammation Diseases 0.000 claims abstract description 4
- 230000004054 inflammatory process Effects 0.000 claims abstract description 4
- 102000053642 Catalytic RNA Human genes 0.000 claims abstract description 3
- 108090000994 Catalytic RNA Proteins 0.000 claims abstract description 3
- 108091092562 ribozyme Proteins 0.000 claims abstract description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 87
- 230000000694 effects Effects 0.000 claims description 78
- 210000004027 cell Anatomy 0.000 claims description 70
- 239000002773 nucleotide Substances 0.000 claims description 50
- 125000003729 nucleotide group Chemical group 0.000 claims description 49
- 239000003795 chemical substances by application Substances 0.000 claims description 46
- 230000004048 modification Effects 0.000 claims description 40
- 238000012986 modification Methods 0.000 claims description 40
- 239000000835 fiber Substances 0.000 claims description 31
- 230000014509 gene expression Effects 0.000 claims description 30
- 108090000623 proteins and genes Proteins 0.000 claims description 28
- -1 triple helix former Proteins 0.000 claims description 28
- 238000001890 transfection Methods 0.000 claims description 26
- 201000011510 cancer Diseases 0.000 claims description 24
- 238000009987 spinning Methods 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 19
- 238000009792 diffusion process Methods 0.000 claims description 18
- 108020004999 messenger RNA Proteins 0.000 claims description 17
- 229920002873 Polyethylenimine Polymers 0.000 claims description 15
- 229920001577 copolymer Polymers 0.000 claims description 15
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 15
- 230000006870 function Effects 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 14
- 239000000758 substrate Substances 0.000 claims description 14
- 210000001519 tissue Anatomy 0.000 claims description 14
- 210000002307 prostate Anatomy 0.000 claims description 13
- 230000000692 anti-sense effect Effects 0.000 claims description 12
- 150000002632 lipids Chemical class 0.000 claims description 12
- 208000015181 infectious disease Diseases 0.000 claims description 11
- 230000007774 longterm Effects 0.000 claims description 11
- 229920001223 polyethylene glycol Polymers 0.000 claims description 11
- 229920000954 Polyglycolide Polymers 0.000 claims description 10
- 239000002246 antineoplastic agent Substances 0.000 claims description 10
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 claims description 10
- 239000004633 polyglycolic acid Substances 0.000 claims description 10
- 229920002451 polyvinyl alcohol Chemical class 0.000 claims description 10
- 102000004169 proteins and genes Human genes 0.000 claims description 10
- PFNFFQXMRSDOHW-UHFFFAOYSA-N spermine Chemical compound NCCCNCCCCNCCCN PFNFFQXMRSDOHW-UHFFFAOYSA-N 0.000 claims description 10
- 210000000481 breast Anatomy 0.000 claims description 9
- 230000015556 catabolic process Effects 0.000 claims description 9
- 229920006317 cationic polymer Polymers 0.000 claims description 9
- 238000006731 degradation reaction Methods 0.000 claims description 9
- 239000004372 Polyvinyl alcohol Chemical class 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 238000002513 implantation Methods 0.000 claims description 8
- 238000003780 insertion Methods 0.000 claims description 8
- 230000037431 insertion Effects 0.000 claims description 8
- 210000000496 pancreas Anatomy 0.000 claims description 8
- 229920000728 polyester Polymers 0.000 claims description 8
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 8
- 235000000346 sugar Nutrition 0.000 claims description 8
- 108020004414 DNA Proteins 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 7
- 210000004204 blood vessel Anatomy 0.000 claims description 7
- 230000001684 chronic effect Effects 0.000 claims description 7
- 230000021615 conjugation Effects 0.000 claims description 7
- 238000003197 gene knockdown Methods 0.000 claims description 7
- 210000001165 lymph node Anatomy 0.000 claims description 7
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 claims description 6
- 239000004698 Polyethylene Substances 0.000 claims description 6
- 239000003146 anticoagulant agent Substances 0.000 claims description 6
- 239000003443 antiviral agent Substances 0.000 claims description 6
- 229920002988 biodegradable polymer Polymers 0.000 claims description 6
- 239000004621 biodegradable polymer Substances 0.000 claims description 6
- 238000005266 casting Methods 0.000 claims description 6
- 125000002091 cationic group Chemical group 0.000 claims description 6
- 210000003238 esophagus Anatomy 0.000 claims description 6
- 239000012528 membrane Substances 0.000 claims description 6
- 229920005615 natural polymer Polymers 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 102000042567 non-coding RNA Human genes 0.000 claims description 6
- 229920000573 polyethylene Polymers 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- 241000282414 Homo sapiens Species 0.000 claims description 5
- 229940035676 analgesics Drugs 0.000 claims description 5
- 239000000730 antalgic agent Substances 0.000 claims description 5
- 229940127219 anticoagulant drug Drugs 0.000 claims description 5
- 210000003445 biliary tract Anatomy 0.000 claims description 5
- 230000015572 biosynthetic process Effects 0.000 claims description 5
- 210000005013 brain tissue Anatomy 0.000 claims description 5
- 235000012000 cholesterol Nutrition 0.000 claims description 5
- 239000003433 contraceptive agent Substances 0.000 claims description 5
- 230000003412 degenerative effect Effects 0.000 claims description 5
- 210000003027 ear inner Anatomy 0.000 claims description 5
- 150000004676 glycans Chemical class 0.000 claims description 5
- 230000002452 interceptive effect Effects 0.000 claims description 5
- 210000004185 liver Anatomy 0.000 claims description 5
- 230000035800 maturation Effects 0.000 claims description 5
- 108091027963 non-coding RNA Proteins 0.000 claims description 5
- 239000002245 particle Substances 0.000 claims description 5
- 229920001282 polysaccharide Polymers 0.000 claims description 5
- 239000005017 polysaccharide Substances 0.000 claims description 5
- 239000010703 silicon Substances 0.000 claims description 5
- 229910052710 silicon Inorganic materials 0.000 claims description 5
- 229940063675 spermine Drugs 0.000 claims description 5
- 238000003786 synthesis reaction Methods 0.000 claims description 5
- 230000002792 vascular Effects 0.000 claims description 5
- 229920001661 Chitosan Polymers 0.000 claims description 4
- 108091036407 Polyadenylation Proteins 0.000 claims description 4
- 229920002472 Starch Polymers 0.000 claims description 4
- 108020004566 Transfer RNA Proteins 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 230000001796 anti-degenerative effect Effects 0.000 claims description 4
- 230000006907 apoptotic process Effects 0.000 claims description 4
- 210000004556 brain Anatomy 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 4
- 229930195729 fatty acid Natural products 0.000 claims description 4
- 239000000194 fatty acid Substances 0.000 claims description 4
- 150000004665 fatty acids Chemical class 0.000 claims description 4
- 239000005556 hormone Substances 0.000 claims description 4
- 229940088597 hormone Drugs 0.000 claims description 4
- 238000002074 melt spinning Methods 0.000 claims description 4
- 239000002679 microRNA Substances 0.000 claims description 4
- 210000003205 muscle Anatomy 0.000 claims description 4
- 230000002093 peripheral effect Effects 0.000 claims description 4
- 239000004626 polylactic acid Substances 0.000 claims description 4
- 229920005594 polymer fiber Polymers 0.000 claims description 4
- 229920002689 polyvinyl acetate Chemical class 0.000 claims description 4
- 230000003405 preventing effect Effects 0.000 claims description 4
- 239000008107 starch Substances 0.000 claims description 4
- 235000019698 starch Nutrition 0.000 claims description 4
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 3
- 108010035532 Collagen Proteins 0.000 claims description 3
- 102000008186 Collagen Human genes 0.000 claims description 3
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 3
- 108090001090 Lectins Proteins 0.000 claims description 3
- 102000004856 Lectins Human genes 0.000 claims description 3
- 108700011259 MicroRNAs Proteins 0.000 claims description 3
- 239000002202 Polyethylene glycol Substances 0.000 claims description 3
- 108091027548 SiDNA Proteins 0.000 claims description 3
- 238000009825 accumulation Methods 0.000 claims description 3
- 230000000202 analgesic effect Effects 0.000 claims description 3
- 230000000340 anti-metabolite Effects 0.000 claims description 3
- 229940121375 antifungal agent Drugs 0.000 claims description 3
- 229960005475 antiinfective agent Drugs 0.000 claims description 3
- 229940100197 antimetabolite Drugs 0.000 claims description 3
- 239000002256 antimetabolite Substances 0.000 claims description 3
- 239000003096 antiparasitic agent Substances 0.000 claims description 3
- 229940125687 antiparasitic agent Drugs 0.000 claims description 3
- 210000001367 artery Anatomy 0.000 claims description 3
- 150000001720 carbohydrates Chemical class 0.000 claims description 3
- 235000014633 carbohydrates Nutrition 0.000 claims description 3
- 239000001913 cellulose Substances 0.000 claims description 3
- 229920002678 cellulose Polymers 0.000 claims description 3
- 229920001436 collagen Polymers 0.000 claims description 3
- 229940124558 contraceptive agent Drugs 0.000 claims description 3
- 238000013270 controlled release Methods 0.000 claims description 3
- 230000032459 dedifferentiation Effects 0.000 claims description 3
- 230000004069 differentiation Effects 0.000 claims description 3
- 229920001971 elastomer Polymers 0.000 claims description 3
- 239000000806 elastomer Substances 0.000 claims description 3
- 230000002496 gastric effect Effects 0.000 claims description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 3
- 239000003018 immunosuppressive agent Substances 0.000 claims description 3
- 230000002401 inhibitory effect Effects 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- 239000002523 lectin Substances 0.000 claims description 3
- 210000004072 lung Anatomy 0.000 claims description 3
- 239000000155 melt Substances 0.000 claims description 3
- 230000017074 necrotic cell death Effects 0.000 claims description 3
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 3
- 229920000962 poly(amidoamine) Polymers 0.000 claims description 3
- 229920000166 polytrimethylene carbonate Polymers 0.000 claims description 3
- 230000003244 pro-oxidative effect Effects 0.000 claims description 3
- 210000000664 rectum Anatomy 0.000 claims description 3
- 230000000241 respiratory effect Effects 0.000 claims description 3
- 239000002993 sponge (artificial) Substances 0.000 claims description 3
- 150000003431 steroids Chemical class 0.000 claims description 3
- 239000003053 toxin Substances 0.000 claims description 3
- 210000003437 trachea Anatomy 0.000 claims description 3
- 238000013519 translation Methods 0.000 claims description 3
- 108091023037 Aptamer Proteins 0.000 claims description 2
- 208000023275 Autoimmune disease Diseases 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 208000035473 Communicable disease Diseases 0.000 claims description 2
- 108091027757 Deoxyribozyme Proteins 0.000 claims description 2
- 108010073385 Fibrin Proteins 0.000 claims description 2
- 102000009123 Fibrin Human genes 0.000 claims description 2
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 claims description 2
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 claims description 2
- 239000004952 Polyamide Chemical class 0.000 claims description 2
- 229920001710 Polyorthoester Polymers 0.000 claims description 2
- 229920001800 Shellac Polymers 0.000 claims description 2
- 230000001154 acute effect Effects 0.000 claims description 2
- 230000000844 anti-bacterial effect Effects 0.000 claims description 2
- 230000001093 anti-cancer Effects 0.000 claims description 2
- 230000002924 anti-infective effect Effects 0.000 claims description 2
- 230000003110 anti-inflammatory effect Effects 0.000 claims description 2
- 210000004227 basal ganglia Anatomy 0.000 claims description 2
- 230000003542 behavioural effect Effects 0.000 claims description 2
- 210000000621 bronchi Anatomy 0.000 claims description 2
- 229940044683 chemotherapy drug Drugs 0.000 claims description 2
- 208000037976 chronic inflammation Diseases 0.000 claims description 2
- 239000002872 contrast media Substances 0.000 claims description 2
- 208000035475 disorder Diseases 0.000 claims description 2
- 229950003499 fibrin Drugs 0.000 claims description 2
- 210000005095 gastrointestinal system Anatomy 0.000 claims description 2
- 210000004884 grey matter Anatomy 0.000 claims description 2
- 229920002674 hyaluronan Polymers 0.000 claims description 2
- 229940099552 hyaluronan Drugs 0.000 claims description 2
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 claims description 2
- 229960003444 immunosuppressant agent Drugs 0.000 claims description 2
- 230000002757 inflammatory effect Effects 0.000 claims description 2
- 229920005610 lignin Polymers 0.000 claims description 2
- 230000003211 malignant effect Effects 0.000 claims description 2
- 210000005036 nerve Anatomy 0.000 claims description 2
- 229920000747 poly(lactic acid) Polymers 0.000 claims description 2
- 229920001281 polyalkylene Polymers 0.000 claims description 2
- 229920002647 polyamide Chemical class 0.000 claims description 2
- 229920000768 polyamine Polymers 0.000 claims description 2
- 229920002643 polyglutamic acid Polymers 0.000 claims description 2
- 239000011118 polyvinyl acetate Chemical class 0.000 claims description 2
- 230000035935 pregnancy Effects 0.000 claims description 2
- 210000003079 salivary gland Anatomy 0.000 claims description 2
- 230000001953 sensory effect Effects 0.000 claims description 2
- 239000004208 shellac Substances 0.000 claims description 2
- 229940113147 shellac Drugs 0.000 claims description 2
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 claims description 2
- 235000013874 shellac Nutrition 0.000 claims description 2
- 230000001743 silencing effect Effects 0.000 claims description 2
- 210000000952 spleen Anatomy 0.000 claims description 2
- 210000000130 stem cell Anatomy 0.000 claims description 2
- 150000008163 sugars Chemical class 0.000 claims description 2
- 230000002889 sympathetic effect Effects 0.000 claims description 2
- 210000003932 urinary bladder Anatomy 0.000 claims description 2
- 238000004073 vulcanization Methods 0.000 claims description 2
- 210000004885 white matter Anatomy 0.000 claims description 2
- 210000002268 wool Anatomy 0.000 claims description 2
- REKYPYSUBKSCAT-UHFFFAOYSA-N 3-hydroxypentanoic acid Chemical compound CCC(O)CC(O)=O REKYPYSUBKSCAT-UHFFFAOYSA-N 0.000 claims 2
- 241000196324 Embryophyta Species 0.000 claims 2
- 230000036772 blood pressure Effects 0.000 claims 2
- 239000001506 calcium phosphate Substances 0.000 claims 2
- 230000000747 cardiac effect Effects 0.000 claims 2
- 230000002254 contraceptive effect Effects 0.000 claims 2
- 239000004205 dimethyl polysiloxane Substances 0.000 claims 2
- 230000002526 effect on cardiovascular system Effects 0.000 claims 2
- 210000003709 heart valve Anatomy 0.000 claims 2
- 238000011540 hip replacement Methods 0.000 claims 2
- 238000007917 intracranial administration Methods 0.000 claims 2
- 238000012806 monitoring device Methods 0.000 claims 2
- 210000000214 mouth Anatomy 0.000 claims 2
- 210000003800 pharynx Anatomy 0.000 claims 2
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims 2
- 229920003229 poly(methyl methacrylate) Polymers 0.000 claims 2
- 229920002627 poly(phosphazenes) Polymers 0.000 claims 2
- 239000004926 polymethyl methacrylate Substances 0.000 claims 2
- 210000002345 respiratory system Anatomy 0.000 claims 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 claims 2
- 229940078499 tricalcium phosphate Drugs 0.000 claims 2
- 229910000391 tricalcium phosphate Inorganic materials 0.000 claims 2
- 235000019731 tricalcium phosphate Nutrition 0.000 claims 2
- 210000001944 turbinate Anatomy 0.000 claims 2
- 230000002485 urinary effect Effects 0.000 claims 2
- 230000002861 ventricular Effects 0.000 claims 2
- KVGZZAHHUNAVKZ-UHFFFAOYSA-N 1,4-Dioxin Chemical compound O1C=COC=C1 KVGZZAHHUNAVKZ-UHFFFAOYSA-N 0.000 claims 1
- KSXTUUUQYQYKCR-LQDDAWAPSA-M 2,3-bis[[(z)-octadec-9-enoyl]oxy]propyl-trimethylazanium;chloride Chemical compound [Cl-].CCCCCCCC\C=C/CCCCCCCC(=O)OCC(C[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC KSXTUUUQYQYKCR-LQDDAWAPSA-M 0.000 claims 1
- AFENDNXGAFYKQO-UHFFFAOYSA-N 2-hydroxybutyric acid Chemical class CCC(O)C(O)=O AFENDNXGAFYKQO-UHFFFAOYSA-N 0.000 claims 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 claims 1
- 108010087765 Antipain Proteins 0.000 claims 1
- 206010011703 Cyanosis Diseases 0.000 claims 1
- 244000089409 Erythrina poeppigiana Species 0.000 claims 1
- 108010010803 Gelatin Proteins 0.000 claims 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 claims 1
- 241000907681 Morpho Species 0.000 claims 1
- 229910019142 PO4 Inorganic materials 0.000 claims 1
- 229920002732 Polyanhydride Polymers 0.000 claims 1
- 235000009776 Rathbunia alamosensis Nutrition 0.000 claims 1
- 241000283984 Rodentia Species 0.000 claims 1
- 229940072056 alginate Drugs 0.000 claims 1
- 229920000615 alginic acid Polymers 0.000 claims 1
- 235000010443 alginic acid Nutrition 0.000 claims 1
- 230000001772 anti-angiogenic effect Effects 0.000 claims 1
- 230000003556 anti-epileptic effect Effects 0.000 claims 1
- 229940124599 anti-inflammatory drug Drugs 0.000 claims 1
- 230000002141 anti-parasite Effects 0.000 claims 1
- 230000000702 anti-platelet effect Effects 0.000 claims 1
- 229940088710 antibiotic agent Drugs 0.000 claims 1
- 239000001961 anticonvulsive agent Substances 0.000 claims 1
- 229940041181 antineoplastic drug Drugs 0.000 claims 1
- SDNYTAYICBFYFH-TUFLPTIASA-N antipain Chemical compound NC(N)=NCCC[C@@H](C=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 SDNYTAYICBFYFH-TUFLPTIASA-N 0.000 claims 1
- 229940121357 antivirals Drugs 0.000 claims 1
- 230000006472 autoimmune response Effects 0.000 claims 1
- 210000000748 cardiovascular system Anatomy 0.000 claims 1
- 239000005018 casein Substances 0.000 claims 1
- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 claims 1
- 235000021240 caseins Nutrition 0.000 claims 1
- 230000004663 cell proliferation Effects 0.000 claims 1
- 235000010980 cellulose Nutrition 0.000 claims 1
- 210000003679 cervix uteri Anatomy 0.000 claims 1
- 230000000973 chemotherapeutic effect Effects 0.000 claims 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 claims 1
- 229960005188 collagen Drugs 0.000 claims 1
- 150000002013 dioxins Chemical class 0.000 claims 1
- 210000003372 endocrine gland Anatomy 0.000 claims 1
- 210000000232 gallbladder Anatomy 0.000 claims 1
- 229920000159 gelatin Polymers 0.000 claims 1
- 239000008273 gelatin Substances 0.000 claims 1
- 229940014259 gelatin Drugs 0.000 claims 1
- 235000019322 gelatine Nutrition 0.000 claims 1
- 235000011852 gelatine desserts Nutrition 0.000 claims 1
- 229930195733 hydrocarbon Natural products 0.000 claims 1
- 150000002430 hydrocarbons Chemical class 0.000 claims 1
- 230000001900 immune effect Effects 0.000 claims 1
- 230000003434 inspiratory effect Effects 0.000 claims 1
- 210000000876 intercostal muscle Anatomy 0.000 claims 1
- 229920000831 ionic polymer Polymers 0.000 claims 1
- 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 1
- 210000001331 nose Anatomy 0.000 claims 1
- 230000003239 periodontal effect Effects 0.000 claims 1
- 238000005191 phase separation Methods 0.000 claims 1
- 239000010452 phosphate Substances 0.000 claims 1
- 150000003904 phospholipids Chemical class 0.000 claims 1
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims 1
- 229920001290 polyvinyl ester Polymers 0.000 claims 1
- 230000003449 preventive effect Effects 0.000 claims 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims 1
- 235000018102 proteins Nutrition 0.000 claims 1
- 229940121896 radiopharmaceutical Drugs 0.000 claims 1
- 239000012217 radiopharmaceutical Substances 0.000 claims 1
- 230000002799 radiopharmaceutical effect Effects 0.000 claims 1
- 238000001338 self-assembly Methods 0.000 claims 1
- 210000003625 skull Anatomy 0.000 claims 1
- 210000000813 small intestine Anatomy 0.000 claims 1
- 239000008247 solid mixture Substances 0.000 claims 1
- 210000002784 stomach Anatomy 0.000 claims 1
- 210000004888 thoracic abdominal cavity Anatomy 0.000 claims 1
- 210000000115 thoracic cavity Anatomy 0.000 claims 1
- YFHICDDUDORKJB-UHFFFAOYSA-N trimethylene carbonate Chemical compound O=C1OCCCO1 YFHICDDUDORKJB-UHFFFAOYSA-N 0.000 claims 1
- 210000000626 ureter Anatomy 0.000 claims 1
- 150000003673 urethanes Chemical class 0.000 claims 1
- 210000003708 urethra Anatomy 0.000 claims 1
- 230000001720 vestibular Effects 0.000 claims 1
- 108020004459 Small interfering RNA Proteins 0.000 abstract description 157
- 239000000463 material Substances 0.000 abstract description 34
- 239000011159 matrix material Substances 0.000 abstract description 17
- 230000009471 action Effects 0.000 abstract description 13
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 abstract description 11
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 abstract description 11
- 210000002744 extracellular matrix Anatomy 0.000 abstract description 11
- 239000002924 silencing RNA Substances 0.000 abstract description 11
- 238000002725 brachytherapy Methods 0.000 abstract description 10
- 230000030279 gene silencing Effects 0.000 abstract description 8
- 239000002184 metal Substances 0.000 abstract description 7
- 229910052751 metal Inorganic materials 0.000 abstract description 7
- 210000000329 smooth muscle myocyte Anatomy 0.000 abstract description 6
- 238000012226 gene silencing method Methods 0.000 abstract description 4
- 108020005544 Antisense RNA Proteins 0.000 abstract description 3
- 239000003184 complementary RNA Substances 0.000 abstract description 3
- 208000024891 symptom Diseases 0.000 abstract description 3
- 230000002708 enhancing effect Effects 0.000 abstract description 2
- 230000001575 pathological effect Effects 0.000 abstract description 2
- 230000005779 cell damage Effects 0.000 abstract 1
- 208000037887 cell injury Diseases 0.000 abstract 1
- 230000007850 degeneration Effects 0.000 abstract 1
- 238000013188 needle biopsy Methods 0.000 abstract 1
- 229940127073 nucleoside analogue Drugs 0.000 abstract 1
- 238000012800 visualization Methods 0.000 abstract 1
- 108060001084 Luciferase Proteins 0.000 description 49
- 239000005089 Luciferase Substances 0.000 description 48
- 238000004020 luminiscence type Methods 0.000 description 35
- 206010061902 Pancreatic neoplasm Diseases 0.000 description 26
- 201000002528 pancreatic cancer Diseases 0.000 description 26
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 description 25
- 208000008443 pancreatic carcinoma Diseases 0.000 description 25
- 239000005090 green fluorescent protein Substances 0.000 description 20
- 238000012360 testing method Methods 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 230000001225 therapeutic effect Effects 0.000 description 16
- 208000026310 Breast neoplasm Diseases 0.000 description 14
- 238000001356 surgical procedure Methods 0.000 description 14
- 206010006187 Breast cancer Diseases 0.000 description 13
- 238000011156 evaluation Methods 0.000 description 13
- 238000002604 ultrasonography Methods 0.000 description 13
- 238000002474 experimental method Methods 0.000 description 12
- 238000002560 therapeutic procedure Methods 0.000 description 12
- RBTBFTRPCNLSDE-UHFFFAOYSA-N 3,7-bis(dimethylamino)phenothiazin-5-ium Chemical compound C1=CC(N(C)C)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 RBTBFTRPCNLSDE-UHFFFAOYSA-N 0.000 description 11
- 238000001727 in vivo Methods 0.000 description 11
- 229960000907 methylthioninium chloride Drugs 0.000 description 11
- 229940124597 therapeutic agent Drugs 0.000 description 11
- 230000003833 cell viability Effects 0.000 description 10
- 230000005764 inhibitory process Effects 0.000 description 10
- 101150105104 Kras gene Proteins 0.000 description 9
- 238000000338 in vitro Methods 0.000 description 9
- 230000004083 survival effect Effects 0.000 description 9
- 206010060862 Prostate cancer Diseases 0.000 description 8
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 8
- 230000001186 cumulative effect Effects 0.000 description 8
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical compound O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 8
- 102000039446 nucleic acids Human genes 0.000 description 8
- 108020004707 nucleic acids Proteins 0.000 description 8
- 150000007523 nucleic acids Chemical class 0.000 description 8
- 238000001262 western blot Methods 0.000 description 8
- 102100023387 Endoribonuclease Dicer Human genes 0.000 description 7
- 239000012097 Lipofectamine 2000 Substances 0.000 description 7
- 102000016943 Muramidase Human genes 0.000 description 7
- 108010014251 Muramidase Proteins 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 7
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 7
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 7
- 210000003712 lysosome Anatomy 0.000 description 7
- 230000001868 lysosomic effect Effects 0.000 description 7
- 239000004325 lysozyme Substances 0.000 description 7
- 229960000274 lysozyme Drugs 0.000 description 7
- 235000010335 lysozyme Nutrition 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 102000040650 (ribonucleotides)n+m Human genes 0.000 description 6
- 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 6
- 102100030708 GTPase KRas Human genes 0.000 description 6
- 101000584612 Homo sapiens GTPase KRas Proteins 0.000 description 6
- 229930195725 Mannitol Natural products 0.000 description 6
- 108091081021 Sense strand Proteins 0.000 description 6
- 239000002260 anti-inflammatory agent Substances 0.000 description 6
- 229940121363 anti-inflammatory agent Drugs 0.000 description 6
- 238000002716 delivery method Methods 0.000 description 6
- 238000009558 endoscopic ultrasound Methods 0.000 description 6
- 230000012010 growth Effects 0.000 description 6
- 239000003102 growth factor Substances 0.000 description 6
- 239000000594 mannitol Substances 0.000 description 6
- 235000010355 mannitol Nutrition 0.000 description 6
- 230000007246 mechanism Effects 0.000 description 6
- 230000005855 radiation Effects 0.000 description 6
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 5
- 101000907904 Homo sapiens Endoribonuclease Dicer Proteins 0.000 description 5
- 208000037396 Intraductal Noninfiltrating Carcinoma Diseases 0.000 description 5
- 101710163270 Nuclease Proteins 0.000 description 5
- 238000001574 biopsy Methods 0.000 description 5
- 239000000872 buffer Substances 0.000 description 5
- 208000028715 ductal breast carcinoma in situ Diseases 0.000 description 5
- 238000003384 imaging method Methods 0.000 description 5
- 239000003112 inhibitor Substances 0.000 description 5
- 229920000139 polyethylene terephthalate Polymers 0.000 description 5
- 239000005020 polyethylene terephthalate Substances 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000001603 reducing effect Effects 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 238000002271 resection Methods 0.000 description 5
- OVONXEQGWXGFJD-UHFFFAOYSA-N 4-sulfanylidene-1h-pyrimidin-2-one Chemical compound SC=1C=CNC(=O)N=1 OVONXEQGWXGFJD-UHFFFAOYSA-N 0.000 description 4
- 229930024421 Adenine Natural products 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- 108091093037 Peptide nucleic acid Proteins 0.000 description 4
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 229960000643 adenine Drugs 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 230000030833 cell death Effects 0.000 description 4
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 4
- 229940127089 cytotoxic agent Drugs 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 230000000857 drug effect Effects 0.000 description 4
- 238000005538 encapsulation Methods 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N glycerol Substances OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000012966 insertion method Methods 0.000 description 4
- 238000002595 magnetic resonance imaging Methods 0.000 description 4
- 239000002121 nanofiber Substances 0.000 description 4
- 239000002105 nanoparticle Substances 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 229920006254 polymer film Polymers 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 102200006539 rs121913529 Human genes 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical compound [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 4
- 229920000428 triblock copolymer Polymers 0.000 description 4
- 230000004614 tumor growth Effects 0.000 description 4
- 229940035893 uracil Drugs 0.000 description 4
- 102000007469 Actins Human genes 0.000 description 3
- 108010085238 Actins Proteins 0.000 description 3
- 206010005003 Bladder cancer Diseases 0.000 description 3
- HMFHBZSHGGEWLO-SOOFDHNKSA-N D-ribofuranose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H]1O HMFHBZSHGGEWLO-SOOFDHNKSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 208000000461 Esophageal Neoplasms Diseases 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 3
- 206010027476 Metastases Diseases 0.000 description 3
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 3
- 229930012538 Paclitaxel Natural products 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- 108700008625 Reporter Genes Proteins 0.000 description 3
- 108010057163 Ribonuclease III Proteins 0.000 description 3
- 102000003661 Ribonuclease III Human genes 0.000 description 3
- PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 3
- 208000019802 Sexually transmitted disease Diseases 0.000 description 3
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 description 3
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 3
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 3
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 3
- 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 3
- 239000000654 additive Substances 0.000 description 3
- HMFHBZSHGGEWLO-UHFFFAOYSA-N alpha-D-Furanose-Ribose Natural products OCC1OC(O)C(O)C1O HMFHBZSHGGEWLO-UHFFFAOYSA-N 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 230000004700 cellular uptake Effects 0.000 description 3
- 238000007385 chemical modification Methods 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 239000002299 complementary DNA Substances 0.000 description 3
- 230000000536 complexating effect Effects 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 231100000517 death Toxicity 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000003745 diagnosis Methods 0.000 description 3
- 238000001839 endoscopy Methods 0.000 description 3
- 230000003628 erosive effect Effects 0.000 description 3
- 201000004101 esophageal cancer Diseases 0.000 description 3
- 229960005277 gemcitabine Drugs 0.000 description 3
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 description 3
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 3
- 210000002216 heart Anatomy 0.000 description 3
- 230000001976 improved effect Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 230000009545 invasion Effects 0.000 description 3
- 230000009401 metastasis Effects 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 229960001592 paclitaxel Drugs 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 229920000724 poly(L-arginine) polymer Polymers 0.000 description 3
- 108010011110 polyarginine Proteins 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 238000011472 radical prostatectomy Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 230000001629 suppression Effects 0.000 description 3
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 3
- 201000005112 urinary bladder cancer Diseases 0.000 description 3
- 239000003981 vehicle Substances 0.000 description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 2
- FZWGECJQACGGTI-UHFFFAOYSA-N 2-amino-7-methyl-1,7-dihydro-6H-purin-6-one Chemical compound NC1=NC(O)=C2N(C)C=NC2=N1 FZWGECJQACGGTI-UHFFFAOYSA-N 0.000 description 2
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 2
- OIVLITBTBDPEFK-UHFFFAOYSA-N 5,6-dihydrouracil Chemical compound O=C1CCNC(=O)N1 OIVLITBTBDPEFK-UHFFFAOYSA-N 0.000 description 2
- RYVNIFSIEDRLSJ-UHFFFAOYSA-N 5-(hydroxymethyl)cytosine Chemical compound NC=1NC(=O)N=CC=1CO RYVNIFSIEDRLSJ-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 2
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 2
- XKJMBINCVNINCA-UHFFFAOYSA-N Alfalone Chemical compound CON(C)C(=O)NC1=CC=C(Cl)C(Cl)=C1 XKJMBINCVNINCA-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 206010049119 Emotional distress Diseases 0.000 description 2
- 102100031780 Endonuclease Human genes 0.000 description 2
- 101710192245 Endoribonuclease Dicer Proteins 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- 101710113436 GTPase KRas Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000031886 HIV Infections Diseases 0.000 description 2
- 208000037357 HIV infectious disease Diseases 0.000 description 2
- 241000711549 Hepacivirus C Species 0.000 description 2
- 206010073094 Intraductal proliferative breast lesion Diseases 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- 239000004472 Lysine Substances 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- 108700020796 Oncogene Proteins 0.000 description 2
- 206010031252 Osteomyelitis Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
- 108010039918 Polylysine Proteins 0.000 description 2
- 229920000388 Polyphosphate Polymers 0.000 description 2
- 102000007066 Prostate-Specific Antigen Human genes 0.000 description 2
- 108010072866 Prostate-Specific Antigen Proteins 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 108010083644 Ribonucleases Proteins 0.000 description 2
- 102000006382 Ribonucleases Human genes 0.000 description 2
- 108010017842 Telomerase Proteins 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 210000000683 abdominal cavity Anatomy 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 238000009098 adjuvant therapy Methods 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 2
- 229960003942 amphotericin b Drugs 0.000 description 2
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000036436 anti-hiv Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 239000003429 antifungal agent Substances 0.000 description 2
- 210000000436 anus Anatomy 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000004900 autophagic degradation Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 238000002591 computed tomography Methods 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 229940111134 coxibs Drugs 0.000 description 2
- 238000007428 craniotomy Methods 0.000 description 2
- 229940097362 cyclodextrins Drugs 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 229940104302 cytosine Drugs 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 229920006237 degradable polymer Polymers 0.000 description 2
- 230000009429 distress Effects 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 210000001163 endosome Anatomy 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000007515 enzymatic degradation Effects 0.000 description 2
- 230000001973 epigenetic effect Effects 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000002575 gastroscopy Methods 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 125000001475 halogen functional group Chemical group 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
- FDGQSTZJBFJUBT-UHFFFAOYSA-N hypoxanthine Chemical compound O=C1NC=NC2=C1NC=N2 FDGQSTZJBFJUBT-UHFFFAOYSA-N 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 230000001394 metastastic effect Effects 0.000 description 2
- 206010061289 metastatic neoplasm Diseases 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 239000000816 peptidomimetic Substances 0.000 description 2
- 210000002640 perineum Anatomy 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 229920000656 polylysine Polymers 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000001205 polyphosphate Substances 0.000 description 2
- 235000011176 polyphosphates Nutrition 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 208000020016 psychiatric disease Diseases 0.000 description 2
- 150000003254 radicals Chemical class 0.000 description 2
- 230000002285 radioactive effect Effects 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 238000003753 real-time PCR Methods 0.000 description 2
- 230000010076 replication Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 229920002631 room-temperature vulcanizate silicone Polymers 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000004706 scrotum Anatomy 0.000 description 2
- 230000003584 silencer Effects 0.000 description 2
- 229960002930 sirolimus Drugs 0.000 description 2
- 229960005322 streptomycin Drugs 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 238000011521 systemic chemotherapy Methods 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 230000005945 translocation Effects 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- BHQCQFFYRZLCQQ-UHFFFAOYSA-N (3alpha,5alpha,7alpha,12alpha)-3,7,12-trihydroxy-cholan-24-oic acid Natural products OC1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 BHQCQFFYRZLCQQ-UHFFFAOYSA-N 0.000 description 1
- QGVQZRDQPDLHHV-DPAQBDIFSA-N (3s,8s,9s,10r,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-3-thiol Chemical compound C1C=C2C[C@@H](S)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 QGVQZRDQPDLHHV-DPAQBDIFSA-N 0.000 description 1
- WGAXJEXVOSVLFY-UHFFFAOYSA-N 1-(2,4-dinitrophenoxy)-2,4-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC([N+](=O)[O-])=CC=C1OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O WGAXJEXVOSVLFY-UHFFFAOYSA-N 0.000 description 1
- AOTQGWFNFTVXNQ-UHFFFAOYSA-N 2-(1-adamantyl)acetic acid Chemical group C1C(C2)CC3CC2CC1(CC(=O)O)C3 AOTQGWFNFTVXNQ-UHFFFAOYSA-N 0.000 description 1
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- MXEMAOPYTXHVEM-UHFFFAOYSA-N 4-methylpent-2-enamide Chemical compound CC(C)C=CC(N)=O MXEMAOPYTXHVEM-UHFFFAOYSA-N 0.000 description 1
- ZLAQATDNGLKIEV-UHFFFAOYSA-N 5-methyl-2-sulfanylidene-1h-pyrimidin-4-one Chemical compound CC1=CNC(=S)NC1=O ZLAQATDNGLKIEV-UHFFFAOYSA-N 0.000 description 1
- LRSASMSXMSNRBT-UHFFFAOYSA-N 5-methylcytosine Chemical compound CC1=CNC(=O)N=C1N LRSASMSXMSNRBT-UHFFFAOYSA-N 0.000 description 1
- JHEKLAXXCHLMNM-UHFFFAOYSA-N 5-propyl-1h-pyrimidine-2,4-dione Chemical compound CCCC1=CNC(=O)NC1=O JHEKLAXXCHLMNM-UHFFFAOYSA-N 0.000 description 1
- DCPSTSVLRXOYGS-UHFFFAOYSA-N 6-amino-1h-pyrimidine-2-thione Chemical compound NC1=CC=NC(S)=N1 DCPSTSVLRXOYGS-UHFFFAOYSA-N 0.000 description 1
- VKKXEIQIGGPMHT-UHFFFAOYSA-N 7h-purine-2,8-diamine Chemical compound NC1=NC=C2NC(N)=NC2=N1 VKKXEIQIGGPMHT-UHFFFAOYSA-N 0.000 description 1
- HRYKDUPGBWLLHO-UHFFFAOYSA-N 8-azaadenine Chemical compound NC1=NC=NC2=NNN=C12 HRYKDUPGBWLLHO-UHFFFAOYSA-N 0.000 description 1
- LPXQRXLUHJKZIE-UHFFFAOYSA-N 8-azaguanine Chemical compound NC1=NC(O)=C2NN=NC2=N1 LPXQRXLUHJKZIE-UHFFFAOYSA-N 0.000 description 1
- 229960005508 8-azaguanine Drugs 0.000 description 1
- FJNCXZZQNBKEJT-UHFFFAOYSA-N 8beta-hydroxymarrubiin Natural products O1C(=O)C2(C)CCCC3(C)C2C1CC(C)(O)C3(O)CCC=1C=COC=1 FJNCXZZQNBKEJT-UHFFFAOYSA-N 0.000 description 1
- MSSXOMSJDRHRMC-UHFFFAOYSA-N 9H-purine-2,6-diamine Chemical compound NC1=NC(N)=C2NC=NC2=N1 MSSXOMSJDRHRMC-UHFFFAOYSA-N 0.000 description 1
- 208000030507 AIDS Diseases 0.000 description 1
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 239000004380 Cholic acid Substances 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108020004635 Complementary DNA Proteins 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 241000723368 Conium Species 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 102000003910 Cyclin D Human genes 0.000 description 1
- 108090000259 Cyclin D Proteins 0.000 description 1
- 108010058546 Cyclin D1 Proteins 0.000 description 1
- 108010058544 Cyclin D2 Proteins 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- BWGNESOTFCXPMA-UHFFFAOYSA-N Dihydrogen disulfide Chemical compound SS BWGNESOTFCXPMA-UHFFFAOYSA-N 0.000 description 1
- 206010059866 Drug resistance Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 101150029707 ERBB2 gene Proteins 0.000 description 1
- 108010042407 Endonucleases Proteins 0.000 description 1
- 102100038595 Estrogen receptor Human genes 0.000 description 1
- 108060002716 Exonuclease Proteins 0.000 description 1
- 102100024165 G1/S-specific cyclin-D1 Human genes 0.000 description 1
- 102100024185 G1/S-specific cyclin-D2 Human genes 0.000 description 1
- 201000010915 Glioblastoma multiforme Diseases 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 208000017891 HER2 positive breast carcinoma Diseases 0.000 description 1
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 description 1
- 244000043261 Hevea brasiliensis Species 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 101000851181 Homo sapiens Epidermal growth factor receptor Proteins 0.000 description 1
- 101000984753 Homo sapiens Serine/threonine-protein kinase B-raf Proteins 0.000 description 1
- UGQMRVRMYYASKQ-UHFFFAOYSA-N Hypoxanthine nucleoside Natural products OC1C(O)C(CO)OC1N1C(NC=NC2=O)=C2N=C1 UGQMRVRMYYASKQ-UHFFFAOYSA-N 0.000 description 1
- 102100034170 Interferon-induced, double-stranded RNA-activated protein kinase Human genes 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 101150078498 MYB gene Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 108091007780 MiR-122 Proteins 0.000 description 1
- 102100038895 Myc proto-oncogene protein Human genes 0.000 description 1
- 101710135898 Myc proto-oncogene protein Proteins 0.000 description 1
- 108010055280 N-hexanoic-Tyr-Ile-(6) aminohexanoic amide Proteins 0.000 description 1
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 description 1
- 206010030180 Oesophageal pain Diseases 0.000 description 1
- 102000043276 Oncogene Human genes 0.000 description 1
- 206010033128 Ovarian cancer Diseases 0.000 description 1
- 206010061535 Ovarian neoplasm Diseases 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 1
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 102000007327 Protamines Human genes 0.000 description 1
- 108010007568 Protamines Proteins 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 108091008611 Protein Kinase B Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 239000012979 RPMI medium Substances 0.000 description 1
- 102000007056 Recombinant Fusion Proteins Human genes 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 206010029107 Respiratory Tract Neoplasms Diseases 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 101100368917 Schizosaccharomyces pombe (strain 972 / ATCC 24843) taz1 gene Proteins 0.000 description 1
- 102100027103 Serine/threonine-protein kinase B-raf Human genes 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229920001963 Synthetic biodegradable polymer Polymers 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 241001116500 Taxus Species 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- 101710150448 Transcriptional regulator Myc Proteins 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010064390 Tumour invasion Diseases 0.000 description 1
- 229910052770 Uranium Inorganic materials 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- HZEWFHLRYVTOIW-UHFFFAOYSA-N [Ti].[Ni] Chemical compound [Ti].[Ni] HZEWFHLRYVTOIW-UHFFFAOYSA-N 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 238000002679 ablation Methods 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 238000011226 adjuvant chemotherapy Methods 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 239000000956 alloy Substances 0.000 description 1
- 229910045601 alloy Inorganic materials 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 229940125644 antibody drug Drugs 0.000 description 1
- 230000007234 antiinflammatory process Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 108010045569 atelocollagen Proteins 0.000 description 1
- 238000011717 athymic nude mouse Methods 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 210000000013 bile duct Anatomy 0.000 description 1
- 238000010876 biochemical test Methods 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 229910052796 boron Inorganic materials 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 238000010804 cDNA synthesis Methods 0.000 description 1
- 230000009400 cancer invasion Effects 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 231100000504 carcinogenesis Toxicity 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 238000002737 cell proliferation kit Methods 0.000 description 1
- 238000002144 chemical decomposition reaction Methods 0.000 description 1
- 238000013189 cholangiography Methods 0.000 description 1
- BHQCQFFYRZLCQQ-OELDTZBJSA-N cholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(O)=O)C)[C@@]2(C)[C@@H](O)C1 BHQCQFFYRZLCQQ-OELDTZBJSA-N 0.000 description 1
- 235000019416 cholic acid Nutrition 0.000 description 1
- 229960002471 cholic acid Drugs 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000007334 copolymerization reaction Methods 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000005520 cutting process Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- INSRQEMEVAMETL-UHFFFAOYSA-N decane-1,1-diol Chemical group CCCCCCCCCC(O)O INSRQEMEVAMETL-UHFFFAOYSA-N 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 229940124447 delivery agent Drugs 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- KXGVEGMKQFWNSR-UHFFFAOYSA-N deoxycholic acid Natural products C1CC2CC(O)CCC2(C)C2C1C1CCC(C(CCC(O)=O)C)C1(C)C(O)C2 KXGVEGMKQFWNSR-UHFFFAOYSA-N 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 239000000645 desinfectant Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 238000009510 drug design Methods 0.000 description 1
- 238000000578 dry spinning Methods 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 201000007273 ductal carcinoma in situ Diseases 0.000 description 1
- 238000004520 electroporation Methods 0.000 description 1
- 238000005421 electrostatic potential Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 238000007459 endoscopic retrograde cholangiopancreatography Methods 0.000 description 1
- 238000012336 endoscopic ultrasonography Methods 0.000 description 1
- 108010048367 enhanced green fluorescent protein Proteins 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 102000013165 exonuclease Human genes 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 238000001943 fluorescence-activated cell sorting Methods 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 230000037440 gene silencing effect Effects 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 208000005017 glioblastoma Diseases 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000002966 glycerophosphoglycerophosphoglycerol group Chemical class 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 201000010536 head and neck cancer Diseases 0.000 description 1
- 208000014829 head and neck neoplasm Diseases 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000012510 hollow fiber Substances 0.000 description 1
- 239000012456 homogeneous solution Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000000879 imine group Chemical group 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000008629 immune suppression Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 230000002584 immunomodulator Effects 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 230000006057 immunotolerant effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000010468 interferon response Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 210000000629 knee joint Anatomy 0.000 description 1
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 125000001921 locked nucleotide group Chemical group 0.000 description 1
- 239000003055 low molecular weight heparin Substances 0.000 description 1
- 229940127215 low-molecular weight heparin Drugs 0.000 description 1
- 210000002751 lymph Anatomy 0.000 description 1
- 239000012139 lysis buffer Substances 0.000 description 1
- 230000005389 magnetism Effects 0.000 description 1
- 230000036210 malignancy Effects 0.000 description 1
- 238000009607 mammography Methods 0.000 description 1
- 230000037323 metabolic rate Effects 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 108091070501 miRNA Proteins 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 239000011259 mixed solution Substances 0.000 description 1
- 239000003607 modifier Substances 0.000 description 1
- 238000009126 molecular therapy Methods 0.000 description 1
- 230000003533 narcotic effect Effects 0.000 description 1
- 229920003052 natural elastomer Polymers 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229920001194 natural rubber Polymers 0.000 description 1
- 238000009099 neoadjuvant therapy Methods 0.000 description 1
- 210000000944 nerve tissue Anatomy 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 229910001000 nickel titanium Inorganic materials 0.000 description 1
- 210000002445 nipple Anatomy 0.000 description 1
- 229920004918 nonoxynol-9 Polymers 0.000 description 1
- 229940087419 nonoxynol-9 Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 229940127234 oral contraceptive Drugs 0.000 description 1
- 239000003539 oral contraceptive agent Substances 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000009116 palliative therapy Methods 0.000 description 1
- 125000000913 palmityl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 description 1
- 210000000277 pancreatic duct Anatomy 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 206010034878 phimosis Diseases 0.000 description 1
- 125000002467 phosphate group Chemical group [H]OP(=O)(O[H])O[*] 0.000 description 1
- 150000004713 phosphodiesters Chemical class 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 1
- 229920000771 poly (alkylcyanoacrylate) Polymers 0.000 description 1
- 239000005014 poly(hydroxyalkanoate) Substances 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920000333 poly(propyleneimine) Polymers 0.000 description 1
- 229920006381 polylactic acid film Polymers 0.000 description 1
- 238000012667 polymer degradation Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 102000003998 progesterone receptors Human genes 0.000 description 1
- 108090000468 progesterone receptors Proteins 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- WJKYOQDIQYJXSD-UHFFFAOYSA-N propan-1-imine Chemical compound CCC=N WJKYOQDIQYJXSD-UHFFFAOYSA-N 0.000 description 1
- 238000011471 prostatectomy Methods 0.000 description 1
- 229940048914 protamine Drugs 0.000 description 1
- 239000000941 radioactive substance Substances 0.000 description 1
- 230000010837 receptor-mediated endocytosis Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 210000003705 ribosome Anatomy 0.000 description 1
- 125000000548 ribosyl group Chemical group C1([C@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 230000011664 signaling Effects 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 229940126586 small molecule drug Drugs 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009331 sowing Methods 0.000 description 1
- 108010068698 spleen exonuclease Proteins 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000003699 striated muscle Anatomy 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- FBWNMEQMRUMQSO-UHFFFAOYSA-N tergitol NP-9 Chemical compound CCCCCCCCCC1=CC=C(OCCOCCOCCOCCOCCOCCOCCOCCOCCO)C=C1 FBWNMEQMRUMQSO-UHFFFAOYSA-N 0.000 description 1
- 238000011191 terminal modification Methods 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- 239000005451 thionucleotide Substances 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 238000003325 tomography Methods 0.000 description 1
- 238000010361 transduction Methods 0.000 description 1
- 230000026683 transduction Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 230000004565 tumor cell growth Effects 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 229940044950 vaginal gel Drugs 0.000 description 1
- 239000000029 vaginal gel Substances 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 230000006444 vascular growth Effects 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 238000002166 wet spinning Methods 0.000 description 1
- 229940075420 xanthine Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
- A61K9/0024—Solid, semi-solid or solidifying implants, which are implanted or injected in body tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Immunology (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US12947708P | 2008-06-30 | 2008-06-30 | |
| US61/129,477 | 2008-06-30 | ||
| PCT/IB2009/052778 WO2010001325A2 (en) | 2008-06-30 | 2009-06-28 | Methods, compositions and systems for local delivery of drugs |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2011526619A true JP2011526619A (ja) | 2011-10-13 |
| JP2011526619A5 JP2011526619A5 (enExample) | 2012-08-30 |
Family
ID=41130308
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011515712A Pending JP2011526619A (ja) | 2008-06-30 | 2009-06-28 | 局所ドラッグデリバリーシステム、その方法、および、その組成物 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US8999945B2 (enExample) |
| EP (1) | EP2323630B1 (enExample) |
| JP (1) | JP2011526619A (enExample) |
| CN (1) | CN102137658A (enExample) |
| AU (1) | AU2009265170A1 (enExample) |
| BR (1) | BRPI0910198A2 (enExample) |
| IL (1) | IL210185A0 (enExample) |
| WO (1) | WO2010001325A2 (enExample) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017538671A (ja) * | 2014-10-23 | 2017-12-28 | シング バイオテクノロジー、エルエルシー | 細胞内抗原に対して指向された単一ドメイン抗体 |
| JP2019010553A (ja) * | 2012-07-06 | 2019-01-24 | クセルティス ベスローテン フェノーツハップXeltis B.V. | インプラント |
| WO2019058333A3 (en) * | 2017-09-22 | 2019-06-27 | Cochlear Limited | Bioactive agent distribution |
| US11370847B2 (en) | 2014-10-23 | 2022-06-28 | Singh Molecular Medicine, Llc | Single domain antibodies directed against intracellular antigens |
| JP2023543267A (ja) * | 2020-09-28 | 2023-10-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | アパルタミドを含有する薬物インプラント及びその使用方法 |
Families Citing this family (94)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2010118238A2 (en) * | 2009-04-08 | 2010-10-14 | Surmodics, Inc. | Controlled release devices and methods for delivery of nucleic acids |
| JP5695035B2 (ja) | 2009-06-03 | 2015-04-01 | フォーサイト・ビジョン5・インコーポレイテッドForsight Vision5,Inc. | 前眼部薬物供給 |
| AU2011208374B2 (en) * | 2010-01-19 | 2016-09-08 | Polypid Ltd. | Sustained-release nucleic acid matrix compositions |
| EP2734261B1 (en) | 2011-07-18 | 2018-02-21 | Mor-Research Applications Ltd. | A device for adjusting the intraocular pressure |
| ES2912370T3 (es) | 2011-09-14 | 2022-05-25 | Forsight Vision5 Inc | Aparato para inserción ocular |
| US9006199B2 (en) | 2011-11-14 | 2015-04-14 | Silenseed Ltd. | Methods and compositions for treating prostate cancer |
| US20130122096A1 (en) | 2011-11-14 | 2013-05-16 | Silenseed Ltd. | Compositions for drug delivery and methods of manufacturing and using same |
| WO2013086419A1 (en) * | 2011-12-09 | 2013-06-13 | California Institute Of Technology | Polymer scaffolds and their use in the treatment of vision loss |
| CN102525935A (zh) * | 2012-01-18 | 2012-07-04 | 上海交通大学医学院 | 一种纳米药物载体脑内递送方法 |
| US8889642B2 (en) | 2012-04-19 | 2014-11-18 | Silenseed Ltd. | Methods and compositions for RNAi-based cancer treatment |
| CN102861341B (zh) * | 2012-09-29 | 2015-06-17 | 张建祥 | 一种能高效负载核酸类药物的复合纳米载体及其制备方法 |
| CN104884006B (zh) | 2012-10-26 | 2017-12-15 | 弗赛特影像5股份有限公司 | 用于持续释放药物到眼睛的眼科系统 |
| WO2014076703A1 (en) * | 2012-11-14 | 2014-05-22 | Silenseed Ltd. | Methods and compositions for treating cancer |
| KR20150105956A (ko) | 2012-12-12 | 2015-09-18 | 더 브로드 인스티튜트, 인코퍼레이티드 | 서열 조작 및 치료적 적용을 위한 시스템, 방법 및 조성물의 전달, 유전자 조작 및 최적화 |
| US10102441B2 (en) * | 2013-02-07 | 2018-10-16 | Vanderbilt University | Methods for automatic segmentation of inner ear anatomy in post-implantation CT and applications of same |
| US9784730B2 (en) | 2013-03-21 | 2017-10-10 | University Of Washington Through Its Center For Commercialization | Nanoparticle for targeting brain tumors and delivery of O6-benzylguanine |
| CN107823721B (zh) * | 2013-05-02 | 2021-01-29 | 德国凯德诺有限责任公司 | 球囊表面涂层 |
| CN107995927B (zh) | 2013-06-17 | 2021-07-30 | 布罗德研究所有限公司 | 用于肝靶向和治疗的crispr-cas系统、载体和组合物的递送与用途 |
| JP6738729B2 (ja) | 2013-06-17 | 2020-08-12 | ザ・ブロード・インスティテュート・インコーポレイテッド | 分裂終了細胞の疾患および障害をターゲティングおよびモデリングするための系、方法および組成物の送達、エンジニアリングおよび最適化 |
| CA2915795C (en) | 2013-06-17 | 2021-07-13 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for targeting disorders and diseases using viral components |
| CN103394128A (zh) * | 2013-08-02 | 2013-11-20 | 苏州市马尔泰新材料有限公司 | 一种含有川芎的模具材料 |
| CN103394127A (zh) * | 2013-08-02 | 2013-11-20 | 苏州市马尔泰新材料有限公司 | 一种含有中西医药的阴道模具材料 |
| BR112016013201B1 (pt) | 2013-12-12 | 2023-01-31 | The Broad Institute, Inc. | Uso de uma composição compreendendo um sistema crispr-cas no tratamento de uma doença genética ocular |
| SG10201804973TA (en) | 2013-12-12 | 2018-07-30 | Broad Inst Inc | Compositions and Methods of Use of Crispr-Cas Systems in Nucleotide Repeat Disorders |
| EP3080271B1 (en) | 2013-12-12 | 2020-02-12 | The Broad Institute, Inc. | Systems, methods and compositions for sequence manipulation with optimized functional crispr-cas systems |
| EP3080259B1 (en) | 2013-12-12 | 2023-02-01 | The Broad Institute, Inc. | Engineering of systems, methods and optimized guide compositions with new architectures for sequence manipulation |
| EP3540051B1 (en) | 2013-12-12 | 2022-08-17 | The Broad Institute, Inc. | Delivery, use and therapeutic applications of the crispr-cas systems and compositions for hsv and viral diseases and disorders. |
| US20170056526A1 (en) * | 2014-02-26 | 2017-03-02 | Ethris Gmbh | Compositions for gastrointestinal administration of rna |
| CN104027848B (zh) * | 2014-06-24 | 2015-10-14 | 中国人民解放军第四军医大学 | 一种用于牙周组织的生物支架材料及其制备方法 |
| US10006030B2 (en) | 2014-07-14 | 2018-06-26 | Silenseed Ltd. | RNA interference compositions targeting heat shock protein 90 and methods of use thereof |
| EP3180426B1 (en) | 2014-08-17 | 2019-12-25 | The Broad Institute, Inc. | Genome editing using cas9 nickases |
| CN106573133B (zh) | 2014-08-19 | 2020-03-03 | 加利福尼亚大学董事会 | 用于局部药物递送的植入物及其使用方法 |
| WO2016049258A2 (en) | 2014-09-25 | 2016-03-31 | The Broad Institute Inc. | Functional screening with optimized functional crispr-cas systems |
| US11033659B2 (en) | 2014-09-29 | 2021-06-15 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of synthesis and use thereof |
| WO2016094880A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Delivery, use and therapeutic applications of crispr systems and compositions for genome editing as to hematopoietic stem cells (hscs) |
| WO2016094872A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Dead guides for crispr transcription factors |
| EP3889260A1 (en) | 2014-12-12 | 2021-10-06 | The Broad Institute, Inc. | Protected guide rnas (pgrnas) |
| WO2016094874A1 (en) | 2014-12-12 | 2016-06-16 | The Broad Institute Inc. | Escorted and functionalized guides for crispr-cas systems |
| EP3234192B1 (en) | 2014-12-19 | 2021-07-14 | The Broad Institute, Inc. | Unbiased identification of double-strand breaks and genomic rearrangement by genome-wide insert capture sequencing |
| WO2016106236A1 (en) | 2014-12-23 | 2016-06-30 | The Broad Institute Inc. | Rna-targeting system |
| EP3237615B2 (en) | 2014-12-24 | 2023-07-26 | The Broad Institute, Inc. | Crispr having or associated with destabilization domains |
| WO2016168141A1 (en) | 2015-04-13 | 2016-10-20 | Forsight Vision5, Inc. | Ocular insert composition of semi-crystalline or crystalline pharmaceutically active agent |
| CA3012631A1 (en) | 2015-06-18 | 2016-12-22 | The Broad Institute Inc. | Novel crispr enzymes and systems |
| AU2016279062A1 (en) | 2015-06-18 | 2019-03-28 | Omar O. Abudayyeh | Novel CRISPR enzymes and systems |
| US9790490B2 (en) | 2015-06-18 | 2017-10-17 | The Broad Institute Inc. | CRISPR enzymes and systems |
| CN109536474A (zh) | 2015-06-18 | 2019-03-29 | 布罗德研究所有限公司 | 降低脱靶效应的crispr酶突变 |
| US11214800B2 (en) | 2015-08-18 | 2022-01-04 | The Broad Institute, Inc. | Methods and compositions for altering function and structure of chromatin loops and/or domains |
| WO2017069958A2 (en) | 2015-10-09 | 2017-04-27 | The Brigham And Women's Hospital, Inc. | Modulation of novel immune checkpoint targets |
| KR102761827B1 (ko) | 2015-10-22 | 2025-02-03 | 더 브로드 인스티튜트, 인코퍼레이티드 | 타입 vi-b crispr 효소 및 시스템 |
| EP3368687B1 (en) | 2015-10-27 | 2021-09-29 | The Broad Institute, Inc. | Compositions and methods for targeting cancer-specific sequence variations |
| EP3368689B1 (en) | 2015-10-28 | 2020-06-17 | The Broad Institute, Inc. | Composition for modulating immune responses by use of immune cell gene signature |
| WO2017075465A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting gata3 |
| WO2017075451A1 (en) | 2015-10-28 | 2017-05-04 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses by detecting and targeting pou2af1 |
| US12110490B2 (en) | 2015-12-18 | 2024-10-08 | The Broad Institute, Inc. | CRISPR enzymes and systems |
| EP3389735B1 (en) | 2015-12-19 | 2022-03-23 | Cardiac Pacemakers, Inc. | Biologically inert coating for implantable medical devices |
| WO2017127473A1 (en) * | 2016-01-19 | 2017-07-27 | The University Of North Carolina At Chapel Hill | Methods and compositions using rna interference for inhibition of kras |
| US11180759B2 (en) | 2016-01-19 | 2021-11-23 | The University Of North Carolina At Chapel Hill | Methods and compositions using RNA interference and antisense oligonucleotides for inhibition of KRAS |
| WO2017189308A1 (en) | 2016-04-19 | 2017-11-02 | The Broad Institute Inc. | Novel crispr enzymes and systems |
| KR102424476B1 (ko) | 2016-04-19 | 2022-07-25 | 더 브로드 인스티튜트, 인코퍼레이티드 | 신규한 crispr 효소 및 시스템 |
| US11286478B2 (en) | 2016-04-19 | 2022-03-29 | The Broad Institute, Inc. | Cpf1 complexes with reduced indel activity |
| US12031235B2 (en) | 2016-04-28 | 2024-07-09 | Amogreentech Co., Ltd. | Nanofiber composite membrane for guided bone regeneration, and manufacturing method therefor |
| WO2017218787A1 (en) | 2016-06-16 | 2017-12-21 | Cardiac Pacemakers, Inc. | Hydrophilization and antifouling of enhanced metal surfaces |
| JP7267013B2 (ja) | 2016-06-17 | 2023-05-01 | ザ・ブロード・インスティテュート・インコーポレイテッド | Vi型crisprオルソログ及び系 |
| US20210222164A1 (en) | 2016-06-29 | 2021-07-22 | The Broad Institute, Inc. | Crispr-cas systems having destabilization domain |
| WO2018017929A1 (en) * | 2016-07-21 | 2018-01-25 | Board Of Regents Of The University Of Nebraska | Ring and tubular structures and methods of synthesis and use thereof |
| WO2018031692A1 (en) | 2016-08-09 | 2018-02-15 | Cardiac Pacemakers, Inc. | Functionalized peg for implantable medical devices |
| WO2018035387A1 (en) | 2016-08-17 | 2018-02-22 | The Broad Institute, Inc. | Novel crispr enzymes and systems |
| US11352647B2 (en) | 2016-08-17 | 2022-06-07 | The Broad Institute, Inc. | Crispr enzymes and systems |
| WO2018049025A2 (en) | 2016-09-07 | 2018-03-15 | The Broad Institute Inc. | Compositions and methods for evaluating and modulating immune responses |
| AU2017335828B2 (en) | 2016-09-28 | 2023-07-13 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of use thereof |
| US12447213B2 (en) | 2016-10-07 | 2025-10-21 | The Broad Institute, Inc. | Modulation of novel immune checkpoint targets |
| WO2018088719A1 (ko) * | 2016-11-09 | 2018-05-17 | 주식회사 삼양바이오팜 | Kras를 표적으로 하는 핵산 함유 약제학적 조성물 및 그 제조방법 |
| EP4361261A3 (en) | 2017-03-15 | 2024-07-10 | The Broad Institute Inc. | Novel cas13b orthologues crispr enzymes and systems |
| CN110799645B (zh) | 2017-04-12 | 2024-08-02 | 博德研究所 | 新型vi型crispr直系同源物和系统 |
| WO2018204777A2 (en) | 2017-05-05 | 2018-11-08 | The Broad Institute, Inc. | Methods for identification and modification of lncrna associated with target genotypes and phenotypes |
| JP2020520961A (ja) | 2017-05-24 | 2020-07-16 | サイレンシード リミテッド | がん免疫療法のための組成物及び方法 |
| WO2018227078A1 (en) | 2017-06-09 | 2018-12-13 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of use thereof |
| CN110168093B (zh) * | 2017-09-12 | 2023-08-15 | 中科蓝华(广州)生物医药技术有限公司 | 一种转染细胞内寄生虫的试剂盒及其应用 |
| AU2018335389B2 (en) | 2017-09-19 | 2023-11-02 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of use thereof |
| WO2019071054A1 (en) | 2017-10-04 | 2019-04-11 | The Broad Institute, Inc. | METHODS AND COMPOSITIONS FOR MODIFYING THE FUNCTION AND STRUCTURE OF BUCKLES AND / OR CHROMATIN DOMAINS |
| WO2019094983A1 (en) | 2017-11-13 | 2019-05-16 | The Broad Institute, Inc. | Methods and compositions for treating cancer by targeting the clec2d-klrb1 pathway |
| US10968257B2 (en) | 2018-04-03 | 2021-04-06 | The Broad Institute, Inc. | Target recognition motifs and uses thereof |
| CA3103983A1 (en) | 2018-06-19 | 2019-12-26 | Biontech Us Inc. | Neoantigens and uses thereof |
| WO2020041380A1 (en) | 2018-08-20 | 2020-02-27 | The Broad Institute, Inc. | Methods and compositions for optochemical control of crispr-cas9 |
| WO2020124072A1 (en) | 2018-12-14 | 2020-06-18 | Board Of Regents Of The University Of Nebraska | Nanofiber structures and methods of manufacture and use thereof |
| WO2020191102A1 (en) | 2019-03-18 | 2020-09-24 | The Broad Institute, Inc. | Type vii crispr proteins and systems |
| JP2022532420A (ja) | 2019-05-17 | 2022-07-14 | サイレンシード リミテッド | 神経周囲浸潤及び疼痛を軽減するための組成物及び方法 |
| JP7295559B2 (ja) * | 2019-06-03 | 2023-06-21 | 国立大学法人 奈良先端科学技術大学院大学 | キトサン系複合体組成物及びキトサン系複合体の製造方法 |
| US11173291B2 (en) | 2020-03-20 | 2021-11-16 | The Regents Of The University Of California | Implantable drug delivery devices for localized drug delivery |
| US11344526B2 (en) | 2020-03-20 | 2022-05-31 | The Regents Of The University Of California | Implantable drug delivery devices for localized drug delivery |
| US11338119B2 (en) | 2020-03-20 | 2022-05-24 | The Regents Of The University Of California | Implantable drug delivery devices for localized drug delivery |
| IT202100021779A1 (it) | 2021-08-11 | 2023-02-11 | Plasfer S R L | Piastrine trasfettate con sirna e loro usi terapeutici |
| TR2021017752A2 (tr) | 2021-11-15 | 2021-12-21 | S D Ue Idari Ve Maliis Dai Bas Genelsekreterlik | Transdermal- i̇laç salim özelli̇kli̇ yeni̇li̇kçi̇ nanoli̇fli̇ medi̇kal teksti̇l malzemesi̇ üreti̇m yöntemi̇ |
| CN114381421B (zh) * | 2022-02-09 | 2023-08-15 | 河北医科大学 | 溶菌酶诱导的小鼠血管平滑肌细胞炎症模型及其建立方法和应用 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040121348A1 (en) * | 2001-10-26 | 2004-06-24 | Ribopharma Ag | Compositions and methods for treating pancreatic cancer |
| WO2007029361A1 (ja) * | 2005-09-02 | 2007-03-15 | Takeda Pharmaceutical Company Limited | 短鎖デオキシリボ核酸又は短鎖リボ核酸含有徐放性マイクロスフェア及びその製造法 |
| JP2008501456A (ja) * | 2004-06-09 | 2008-01-24 | イェー・アー・ツェー・ツェー・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | インプラント可能な装置 |
| WO2008057867A2 (en) * | 2006-11-03 | 2008-05-15 | Allergan, Inc. | Sustained release drug delivery systems comprising a water soluble therapeutic agent and a release modifier |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3687808A (en) | 1969-08-14 | 1972-08-29 | Univ Leland Stanford Junior | Synthetic polynucleotides |
| US5801154A (en) * | 1993-10-18 | 1998-09-01 | Isis Pharmaceuticals, Inc. | Antisense oligonucleotide modulation of multidrug resistance-associated protein |
| JPH09124490A (ja) | 1995-10-27 | 1997-05-13 | Eisai Co Ltd | ヌクレオチド含有製剤 |
| US6303374B1 (en) | 2000-01-18 | 2001-10-16 | Isis Pharmaceuticals Inc. | Antisense modulation of caspase 3 expression |
| AU2001265252A1 (en) | 2000-05-31 | 2001-12-11 | The Johns-Hopkins University | Biologically useful polyphosphates |
| US7427394B2 (en) | 2000-10-10 | 2008-09-23 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US6998115B2 (en) | 2000-10-10 | 2006-02-14 | Massachusetts Institute Of Technology | Biodegradable poly(β-amino esters) and uses thereof |
| US6514193B2 (en) * | 2000-11-16 | 2003-02-04 | Microspherix Llc | Method of administering a therapeutically active substance |
| US6812217B2 (en) | 2000-12-04 | 2004-11-02 | Medtronic, Inc. | Medical device and methods of use |
| US20040063654A1 (en) * | 2001-11-02 | 2004-04-01 | Davis Mark E. | Methods and compositions for therapeutic use of RNA interference |
| US20060160759A1 (en) * | 2002-09-28 | 2006-07-20 | Jianzhu Chen | Influenza therapeutic |
| US20070207211A1 (en) * | 2003-04-10 | 2007-09-06 | Pr Pharmaceuticals, Inc. | Emulsion-based microparticles and methods for the production thereof |
| US20060228404A1 (en) * | 2004-03-04 | 2006-10-12 | Anderson Daniel G | Compositions and methods for treatment of hypertrophic tissues |
| EP1807514A1 (en) * | 2004-10-22 | 2007-07-18 | Benitec, Inc. | Therapeutic rnai agents for treating psoriasis |
| EP1679065A1 (en) * | 2005-01-07 | 2006-07-12 | OctoPlus Sciences B.V. | Controlled release compositions for interferon based on PEGT/PBT block copolymers |
| CA2631082C (en) * | 2005-11-23 | 2015-02-03 | Board Of Regents Of The University Of Texas System | Oncogenic ras-specific cytotoxic compound and methods of use thereof |
| US8138160B2 (en) | 2006-08-03 | 2012-03-20 | Warsaw Orthopedic, Inc. | Reagents, methods and systems to suppress pro-inflammatory cytokines |
| US8936794B2 (en) * | 2006-08-25 | 2015-01-20 | The Regents Of The University Of Michigan | Conducting polymer nanotube actuators for precisely controlled release of medicine and bioactive molecules |
| US20080213377A1 (en) | 2006-12-08 | 2008-09-04 | Bhatia Sangeeta N | Delivery of Nanoparticles and/or Agents to Cells |
| WO2008124634A1 (en) * | 2007-04-04 | 2008-10-16 | Massachusetts Institute Of Technology | Polymer-encapsulated reverse micelles |
| US20090149569A1 (en) * | 2007-07-19 | 2009-06-11 | Shastri V Prasad | Surface engineering of tissue graft materials for enhanced porosity and cell adhesion |
-
2009
- 2009-06-28 US US13/000,656 patent/US8999945B2/en active Active
- 2009-06-28 EP EP09772985.9A patent/EP2323630B1/en active Active
- 2009-06-28 JP JP2011515712A patent/JP2011526619A/ja active Pending
- 2009-06-28 AU AU2009265170A patent/AU2009265170A1/en not_active Abandoned
- 2009-06-28 BR BRPI0910198A patent/BRPI0910198A2/pt not_active Application Discontinuation
- 2009-06-28 WO PCT/IB2009/052778 patent/WO2010001325A2/en not_active Ceased
- 2009-06-28 CN CN2009801337306A patent/CN102137658A/zh active Pending
-
2010
- 2010-12-22 IL IL210185A patent/IL210185A0/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040121348A1 (en) * | 2001-10-26 | 2004-06-24 | Ribopharma Ag | Compositions and methods for treating pancreatic cancer |
| JP2008501456A (ja) * | 2004-06-09 | 2008-01-24 | イェー・アー・ツェー・ツェー・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | インプラント可能な装置 |
| WO2007029361A1 (ja) * | 2005-09-02 | 2007-03-15 | Takeda Pharmaceutical Company Limited | 短鎖デオキシリボ核酸又は短鎖リボ核酸含有徐放性マイクロスフェア及びその製造法 |
| WO2008057867A2 (en) * | 2006-11-03 | 2008-05-15 | Allergan, Inc. | Sustained release drug delivery systems comprising a water soluble therapeutic agent and a release modifier |
Non-Patent Citations (1)
| Title |
|---|
| JPN6014041519; 遺伝子医学 Vol.6,No.1, 2002, p.21-25 * |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019010553A (ja) * | 2012-07-06 | 2019-01-24 | クセルティス ベスローテン フェノーツハップXeltis B.V. | インプラント |
| JP2017538671A (ja) * | 2014-10-23 | 2017-12-28 | シング バイオテクノロジー、エルエルシー | 細胞内抗原に対して指向された単一ドメイン抗体 |
| US11370847B2 (en) | 2014-10-23 | 2022-06-28 | Singh Molecular Medicine, Llc | Single domain antibodies directed against intracellular antigens |
| WO2019058333A3 (en) * | 2017-09-22 | 2019-06-27 | Cochlear Limited | Bioactive agent distribution |
| US12285590B2 (en) | 2017-09-22 | 2025-04-29 | Cochlear Limited | Bioactive agent distribution |
| JP2023543267A (ja) * | 2020-09-28 | 2023-10-13 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | アパルタミドを含有する薬物インプラント及びその使用方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| IL210185A0 (en) | 2011-03-31 |
| EP2323630A2 (en) | 2011-05-25 |
| BRPI0910198A2 (pt) | 2016-01-12 |
| US20110195123A1 (en) | 2011-08-11 |
| WO2010001325A3 (en) | 2010-12-02 |
| EP2323630B1 (en) | 2014-11-19 |
| WO2010001325A2 (en) | 2010-01-07 |
| CN102137658A (zh) | 2011-07-27 |
| AU2009265170A1 (en) | 2010-01-07 |
| US8999945B2 (en) | 2015-04-07 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8999945B2 (en) | Methods, compositions and systems for local delivery of drugs | |
| Pinese et al. | Sustained delivery of siRNA/mesoporous silica nanoparticle complexes from nanofiber scaffolds for long-term gene silencing | |
| ES2871029T3 (es) | Dispositivos de liberación de fármacos recargables y procedimientos de uso de los mismos | |
| EP2591770B1 (en) | Compositions for siRNA delivery and methods of manufacturing and using same | |
| Ding et al. | A self-assembled RNA-triple helix hydrogel drug delivery system targeting triple-negative breast cancer | |
| CN107614685B (zh) | Rna纳米颗粒及其使用方法 | |
| O’Rorke et al. | Non-viral polyplexes: Scaffold mediated delivery for gene therapy | |
| Balaji et al. | An insight on electrospun-nanofibers-inspired modern drug delivery system in the treatment of deadly cancers | |
| JP6232487B2 (ja) | 内耳感覚有毛細胞の再生または置換のための組成物および方法 | |
| Hu et al. | Effective antitumor gene therapy delivered by polyethylenimine-conjugated stearic acid-g-chitosan oligosaccharide micelles | |
| EP2805713B1 (en) | Magnetic nanoparticle-samirna complex and method for preparing same | |
| JP2021107420A (ja) | 埋込み型薬物送達組成物およびその使用法 | |
| US20180021441A1 (en) | Hyperbranched polymers and polyplexes and dna or rna delivery systems including the same | |
| AU2017389100B2 (en) | Complex for drug delivery and stabilization and preparation method thereof | |
| CN112368382A (zh) | 用于预防和治疗纤维化相关疾病和呼吸系统疾病的双调蛋白基因特异性双链寡核苷酸和包含其的组合物 | |
| US20210154149A1 (en) | Transfection reagents for delivery of nucleic acids | |
| Kim et al. | Tumor-suppressing miR-141 gene complex-loaded tissue-adhesive glue for the locoregional treatment of hepatocellular carcinoma | |
| Zhu et al. | A doxorubicin and siRNA coloaded nanolamellar hydroxyapatite/PLGA electrospun scaffold as a safe antitumor drug delivery system | |
| EP2790739A1 (en) | Nanoparticles and uses thereof | |
| Meng et al. | An injectable miRNA-activated matrix for effective bone regeneration in vivo | |
| EP4634386A1 (en) | Antisense oligonucleotide analogs of mir-29 and uses thereof | |
| CN117677402A (zh) | 用于使用超声雾化器施用用于预防或治疗包括covid-19的呼吸道病毒感染、由病毒感染引起的肺纤维化或呼吸道疾病的双链寡核苷酸结构的组合物 | |
| Ye et al. | Preliminary preclinical study of Chol-DsiRNA polyplexes formed with PLL [30]-PEG [5K] for the RNAi-based therapy of breast cancer | |
| Keyvani et al. | Insight into RNA-based Therapies for Ovarian Cancer | |
| Paulmurugan et al. | Biodegradable polymer nanocarriers for therapeutic antisense microRNA delivery in living animals |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20120625 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20120628 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20120628 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20120625 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20131022 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20131022 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20140122 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20140129 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140224 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20141007 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20141218 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150129 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20150623 |