CA2838289C - Sustained release formulations for delivery of proteins to the eye and methods of preparing same - Google Patents
Sustained release formulations for delivery of proteins to the eye and methods of preparing same Download PDFInfo
- Publication number
- CA2838289C CA2838289C CA2838289A CA2838289A CA2838289C CA 2838289 C CA2838289 C CA 2838289C CA 2838289 A CA2838289 A CA 2838289A CA 2838289 A CA2838289 A CA 2838289A CA 2838289 C CA2838289 C CA 2838289C
- Authority
- CA
- Canada
- Prior art keywords
- formulation
- liquid
- plga
- inhibits
- 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.)
- Active
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 177
- 238000009472 formulation Methods 0.000 title claims abstract description 166
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 54
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 54
- 238000013268 sustained release Methods 0.000 title claims abstract description 45
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 45
- 238000012384 transportation and delivery Methods 0.000 title abstract description 4
- 238000000034 method Methods 0.000 title description 12
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims abstract description 106
- 239000007788 liquid Substances 0.000 claims abstract description 65
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 57
- 229920000642 polymer Polymers 0.000 claims abstract description 56
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 36
- WEAPVABOECTMGR-UHFFFAOYSA-N triethyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCOC(=O)CC(C(=O)OCC)(OC(C)=O)CC(=O)OCC WEAPVABOECTMGR-UHFFFAOYSA-N 0.000 claims description 122
- SESFRYSPDFLNCH-UHFFFAOYSA-N benzyl benzoate Chemical group C=1C=CC=CC=1C(=O)OCC1=CC=CC=C1 SESFRYSPDFLNCH-UHFFFAOYSA-N 0.000 claims description 42
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 29
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 29
- 238000002347 injection Methods 0.000 claims description 24
- 239000007924 injection Substances 0.000 claims description 24
- 229960002903 benzyl benzoate Drugs 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 239000001069 triethyl citrate Substances 0.000 claims description 16
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 claims description 16
- 235000013769 triethyl citrate Nutrition 0.000 claims description 16
- 125000005907 alkyl ester group Chemical group 0.000 claims description 13
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 8
- 230000033115 angiogenesis Effects 0.000 claims description 8
- 239000012669 liquid formulation Substances 0.000 claims description 7
- 208000006386 Bone Resorption Diseases 0.000 claims description 5
- 230000024279 bone resorption Effects 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- 230000004614 tumor growth Effects 0.000 claims description 5
- 210000002159 anterior chamber Anatomy 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 abstract description 22
- 239000013543 active substance Substances 0.000 abstract description 21
- 229920002988 biodegradable polymer Polymers 0.000 abstract 1
- 239000004621 biodegradable polymer Substances 0.000 abstract 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 71
- 229960003957 dexamethasone Drugs 0.000 description 71
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
- 230000002459 sustained effect Effects 0.000 description 27
- -1 citrate ester Chemical class 0.000 description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 238000000338 in vitro Methods 0.000 description 20
- 238000011282 treatment Methods 0.000 description 17
- 208000035475 disorder Diseases 0.000 description 14
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 229920000747 poly(lactic acid) Polymers 0.000 description 9
- 108010025020 Nerve Growth Factor Proteins 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 8
- 150000002148 esters Chemical group 0.000 description 8
- 239000011159 matrix material Substances 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- HHVIBTZHLRERCL-UHFFFAOYSA-N sulfonyldimethane Chemical compound CS(C)(=O)=O HHVIBTZHLRERCL-UHFFFAOYSA-N 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 7
- 208000024891 symptom Diseases 0.000 description 7
- 102000004127 Cytokines Human genes 0.000 description 6
- 108090000695 Cytokines Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 102000007072 Nerve Growth Factors Human genes 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000000427 antigen Substances 0.000 description 6
- 108091007433 antigens Proteins 0.000 description 6
- 102000036639 antigens Human genes 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 5
- 229920001244 Poly(D,L-lactide) Polymers 0.000 description 5
- 206010064930 age-related macular degeneration Diseases 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000007943 implant Substances 0.000 description 5
- 208000002780 macular degeneration Diseases 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- BBMCTIGTTCKYKF-UHFFFAOYSA-N 1-heptanol Chemical compound CCCCCCCO BBMCTIGTTCKYKF-UHFFFAOYSA-N 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 4
- 206010029113 Neovascularisation Diseases 0.000 description 4
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- 229920000954 Polyglycolide Polymers 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- MWKFXSUHUHTGQN-UHFFFAOYSA-N decan-1-ol Chemical compound CCCCCCCCCCO MWKFXSUHUHTGQN-UHFFFAOYSA-N 0.000 description 4
- 150000005690 diesters Chemical class 0.000 description 4
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 4
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 4
- ZWRUINPWMLAQRD-UHFFFAOYSA-N nonan-1-ol Chemical compound CCCCCCCCCO ZWRUINPWMLAQRD-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 150000005691 triesters Chemical class 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZAKOWWREFLAJOT-CEFNRUSXSA-N D-alpha-tocopherylacetate Chemical compound CC(=O)OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-CEFNRUSXSA-N 0.000 description 3
- QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 3
- 208000010412 Glaucoma Diseases 0.000 description 3
- 108060003951 Immunoglobulin Proteins 0.000 description 3
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 210000003161 choroid Anatomy 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 102000018358 immunoglobulin Human genes 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 239000003900 neurotrophic factor Substances 0.000 description 3
- 108090000102 pigment epithelium-derived factor Proteins 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 238000005070 sampling Methods 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 150000003612 tocotrienol derivatives Chemical class 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 2
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 2
- 108010011459 Exenatide Proteins 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 2
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 2
- 108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 2
- 102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 2
- 101001112429 Homo sapiens Serine hydrolase RBBP9 Proteins 0.000 description 2
- 102000004877 Insulin Human genes 0.000 description 2
- 108090001061 Insulin Proteins 0.000 description 2
- 102000003996 Interferon-beta Human genes 0.000 description 2
- 108090000467 Interferon-beta Proteins 0.000 description 2
- 102000008070 Interferon-gamma Human genes 0.000 description 2
- 108010074328 Interferon-gamma Proteins 0.000 description 2
- 102000014150 Interferons Human genes 0.000 description 2
- 108010050904 Interferons Proteins 0.000 description 2
- 108010002350 Interleukin-2 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-Lactic acid Natural products C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 2
- 102000015336 Nerve Growth Factor Human genes 0.000 description 2
- 108090000099 Neurotrophin-4 Proteins 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000034530 PLAA-associated neurodevelopmental disease Diseases 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000001931 aliphatic group Chemical group 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000001772 anti-angiogenic effect Effects 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 230000000840 anti-viral effect Effects 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 239000004599 antimicrobial Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229940066595 beta tocopherol Drugs 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000000423 cell based assay Methods 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 2
- ZAKOWWREFLAJOT-UHFFFAOYSA-N d-alpha-Tocopheryl acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C ZAKOWWREFLAJOT-UHFFFAOYSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- 229940052296 esters of benzoic acid for local anesthesia Drugs 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 108010074605 gamma-Globulins Proteins 0.000 description 2
- FOYKKGHVWRFIBD-UHFFFAOYSA-N gamma-tocopherol acetate Natural products CC(=O)OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 FOYKKGHVWRFIBD-UHFFFAOYSA-N 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000009169 immunotherapy Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000000099 in vitro assay Methods 0.000 description 2
- 238000005462 in vivo assay Methods 0.000 description 2
- 229940125396 insulin Drugs 0.000 description 2
- 229960003130 interferon gamma Drugs 0.000 description 2
- 229960001388 interferon-beta Drugs 0.000 description 2
- 229940047124 interferons Drugs 0.000 description 2
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- KPSSIOMAKSHJJG-UHFFFAOYSA-N neopentyl alcohol Chemical compound CC(C)(C)CO KPSSIOMAKSHJJG-UHFFFAOYSA-N 0.000 description 2
- 230000001414 neuropoietic effect Effects 0.000 description 2
- 230000000508 neurotrophic effect Effects 0.000 description 2
- 235000001968 nicotinic acid Nutrition 0.000 description 2
- 239000011664 nicotinic acid Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000001575 pathological effect Effects 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004196 processed proteins & peptides Human genes 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000012134 supernatant fraction Substances 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 229960000984 tocofersolan Drugs 0.000 description 2
- AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- TUUQISRYLMFKOG-UHFFFAOYSA-N trihexyl 2-acetyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(C)=O)CC(=O)OCCCCCC TUUQISRYLMFKOG-UHFFFAOYSA-N 0.000 description 2
- GWVUTNGDMGTPFE-UHFFFAOYSA-N trihexyl 2-butanoyloxypropane-1,2,3-tricarboxylate Chemical compound CCCCCCOC(=O)CC(C(=O)OCCCCCC)(OC(=O)CCC)CC(=O)OCCCCCC GWVUTNGDMGTPFE-UHFFFAOYSA-N 0.000 description 2
- 102000003390 tumor necrosis factor Human genes 0.000 description 2
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 2
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- 239000002076 α-tocopherol Substances 0.000 description 2
- 235000004835 α-tocopherol Nutrition 0.000 description 2
- 239000011590 β-tocopherol Substances 0.000 description 2
- WGVKWNUPNGFDFJ-DQCZWYHMSA-N β-tocopherol Chemical compound OC1=CC(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C WGVKWNUPNGFDFJ-DQCZWYHMSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JJTUDXZGHPGLLC-IMJSIDKUSA-N 4511-42-6 Chemical compound C[C@@H]1OC(=O)[C@H](C)OC1=O JJTUDXZGHPGLLC-IMJSIDKUSA-N 0.000 description 1
- 108010088751 Albumins Proteins 0.000 description 1
- 102000009027 Albumins Human genes 0.000 description 1
- 102400000068 Angiostatin Human genes 0.000 description 1
- 108010079709 Angiostatins Proteins 0.000 description 1
- 108010032595 Antibody Binding Sites Proteins 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- 108090000715 Brain-derived neurotrophic factor Proteins 0.000 description 1
- 102000004219 Brain-derived neurotrophic factor Human genes 0.000 description 1
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- 108010029697 CD40 Ligand Proteins 0.000 description 1
- 102100032937 CD40 ligand Human genes 0.000 description 1
- 208000016623 Choroid neoplasm Diseases 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 108010032597 Cohn fraction II Proteins 0.000 description 1
- 108010044316 Cohn fraction III Proteins 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 206010011715 Cyclitis Diseases 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 102400001047 Endostatin Human genes 0.000 description 1
- 108010079505 Endostatins Proteins 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 1
- 102000034615 Glial cell line-derived neurotrophic factor Human genes 0.000 description 1
- 108091010837 Glial cell line-derived neurotrophic factor Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 1
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 1
- 239000000579 Gonadotropin-Releasing Hormone Substances 0.000 description 1
- 229940122853 Growth hormone antagonist Drugs 0.000 description 1
- 108010022901 Heparin Lyase Proteins 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 101000976075 Homo sapiens Insulin Proteins 0.000 description 1
- 101000851018 Homo sapiens Vascular endothelial growth factor receptor 1 Proteins 0.000 description 1
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 108010002352 Interleukin-1 Proteins 0.000 description 1
- 102000000589 Interleukin-1 Human genes 0.000 description 1
- 108090000174 Interleukin-10 Proteins 0.000 description 1
- 108010065805 Interleukin-12 Proteins 0.000 description 1
- 108090000172 Interleukin-15 Proteins 0.000 description 1
- 108090000171 Interleukin-18 Proteins 0.000 description 1
- 108090000978 Interleukin-4 Proteins 0.000 description 1
- 108010002616 Interleukin-5 Proteins 0.000 description 1
- 108090001005 Interleukin-6 Proteins 0.000 description 1
- 108010002586 Interleukin-7 Proteins 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 206010065630 Iris neovascularisation Diseases 0.000 description 1
- 108010041872 Islet Amyloid Polypeptide Proteins 0.000 description 1
- 102000036770 Islet Amyloid Polypeptide Human genes 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 102400001103 Neurotensin Human genes 0.000 description 1
- 101800001814 Neurotensin Proteins 0.000 description 1
- 102000004230 Neurotrophin 3 Human genes 0.000 description 1
- 108090000742 Neurotrophin 3 Proteins 0.000 description 1
- 102000003683 Neurotrophin-4 Human genes 0.000 description 1
- 102100033857 Neurotrophin-4 Human genes 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 201000010183 Papilledema Diseases 0.000 description 1
- 108010033276 Peptide Fragments Proteins 0.000 description 1
- 102000007079 Peptide Fragments Human genes 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 1
- 108090000778 Platelet factor 4 Proteins 0.000 description 1
- 102000004211 Platelet factor 4 Human genes 0.000 description 1
- 239000004743 Polypropylene Substances 0.000 description 1
- 201000002154 Pterygium Diseases 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 208000016624 Retinal neoplasm Diseases 0.000 description 1
- 206010038886 Retinal oedema Diseases 0.000 description 1
- 208000032400 Retinal pigmentation Diseases 0.000 description 1
- 208000014139 Retinal vascular disease Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 229940127395 Ribonucleotide Reductase Inhibitors Drugs 0.000 description 1
- 101000857870 Squalus acanthias Gonadoliberin Proteins 0.000 description 1
- 102000005406 Tissue Inhibitor of Metalloproteinase-3 Human genes 0.000 description 1
- 108010031429 Tissue Inhibitor of Metalloproteinase-3 Proteins 0.000 description 1
- 102000009618 Transforming Growth Factors Human genes 0.000 description 1
- 108010009583 Transforming Growth Factors Proteins 0.000 description 1
- 206010047050 Vascular anomaly Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 208000037919 acquired disease Diseases 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 229940121359 adenosine receptor antagonist Drugs 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000003288 aldose reductase inhibitor Substances 0.000 description 1
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 229920003232 aliphatic polyester Polymers 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000000964 angiostatic effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003712 anti-aging effect Effects 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940044684 anti-microtubule agent Drugs 0.000 description 1
- 230000002141 anti-parasite Effects 0.000 description 1
- 230000001494 anti-thymocyte effect Effects 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 239000000030 antiglaucoma agent Substances 0.000 description 1
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000003096 antiparasitic agent Substances 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229940121383 antituberculosis agent Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 1
- 239000012131 assay buffer Substances 0.000 description 1
- 229960004669 basiliximab Drugs 0.000 description 1
- 229960005347 belatacept Drugs 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940030611 beta-adrenergic blocking agent Drugs 0.000 description 1
- 229960000397 bevacizumab Drugs 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000008238 biochemical pathway Effects 0.000 description 1
- 229920000229 biodegradable polyester Polymers 0.000 description 1
- 239000004622 biodegradable polyester Substances 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229940077737 brain-derived neurotrophic factor Drugs 0.000 description 1
- 229940084891 byetta Drugs 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 201000002588 choroid cancer Diseases 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000001886 ciliary effect Effects 0.000 description 1
- 238000011281 clinical therapy Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000013267 controlled drug release Methods 0.000 description 1
- 238000011443 conventional therapy Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 231100000599 cytotoxic agent Toxicity 0.000 description 1
- 239000002619 cytotoxin Substances 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 108700014844 flt3 ligand Proteins 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000013467 fragmentation Methods 0.000 description 1
- 238000006062 fragmentation reaction Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000005714 functional activity Effects 0.000 description 1
- 230000000574 ganglionic effect Effects 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- XLXSAKCOAKORKW-AQJXLSMYSA-N gonadorelin Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)NCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 XLXSAKCOAKORKW-AQJXLSMYSA-N 0.000 description 1
- 229940035638 gonadotropin-releasing hormone Drugs 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002519 immonomodulatory effect Effects 0.000 description 1
- 239000002955 immunomodulating agent Substances 0.000 description 1
- 229940121354 immunomodulator Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 229960000598 infliximab Drugs 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 229950010470 lerdelimumab Drugs 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 229940076783 lucentis Drugs 0.000 description 1
- 229940040129 luteinizing hormone Drugs 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000035800 maturation Effects 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002077 nanosphere Substances 0.000 description 1
- 239000004081 narcotic agent Substances 0.000 description 1
- 201000003142 neovascular glaucoma Diseases 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- PCJGZPGTCUMMOT-ISULXFBGSA-N neurotensin Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 PCJGZPGTCUMMOT-ISULXFBGSA-N 0.000 description 1
- 229940032018 neurotrophin 3 Drugs 0.000 description 1
- 229940097998 neurotrophin 4 Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000006508 oncogene activation Effects 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229940026778 other chemotherapeutics in atc Drugs 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000000296 purinergic P1 receptor antagonist Substances 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000003488 releasing hormone Substances 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 201000011195 retinal edema Diseases 0.000 description 1
- 239000012898 sample dilution Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 238000009121 systemic therapy Methods 0.000 description 1
- 239000003277 telomerase inhibitor Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000017423 tissue regeneration Effects 0.000 description 1
- 239000011732 tocopherol Substances 0.000 description 1
- 229930003799 tocopherol Natural products 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- 235000019149 tocopherols Nutrition 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000000814 tuberculostatic agent Substances 0.000 description 1
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 1
- 210000005166 vasculature Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 208000026726 vitreous disease Diseases 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/39541—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against normal tissues, cells
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
-
- 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
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/20—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
-
- 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
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- 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
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Ophthalmology & Optometry (AREA)
- Marine Sciences & Fisheries (AREA)
- Inorganic Chemistry (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurosurgery (AREA)
- Dermatology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Rheumatology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161495672P | 2011-06-10 | 2011-06-10 | |
| US61/495,672 | 2011-06-10 | ||
| PCT/US2012/041950 WO2013036309A2 (en) | 2011-06-10 | 2012-06-11 | Sustained release formulations for delivery of proteins to the eye and methods of preparing same |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2838289A1 CA2838289A1 (en) | 2013-03-14 |
| CA2838289C true CA2838289C (en) | 2019-09-10 |
Family
ID=47832748
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2838289A Active CA2838289C (en) | 2011-06-10 | 2012-06-11 | Sustained release formulations for delivery of proteins to the eye and methods of preparing same |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US9814773B2 (enExample) |
| EP (1) | EP2717914B1 (enExample) |
| JP (1) | JP6339011B2 (enExample) |
| KR (1) | KR20140060274A (enExample) |
| CN (1) | CN103945865B (enExample) |
| AU (1) | AU2012304909B2 (enExample) |
| BR (1) | BR112013031685B1 (enExample) |
| CA (1) | CA2838289C (enExample) |
| CY (1) | CY1122771T1 (enExample) |
| DK (1) | DK2717914T3 (enExample) |
| ES (1) | ES2761340T3 (enExample) |
| HR (1) | HRP20192276T1 (enExample) |
| HU (1) | HUE047737T2 (enExample) |
| IN (1) | IN2013MN02384A (enExample) |
| LT (1) | LT2717914T (enExample) |
| MX (1) | MX359119B (enExample) |
| PL (1) | PL2717914T3 (enExample) |
| PT (1) | PT2717914T (enExample) |
| RS (1) | RS60051B1 (enExample) |
| SI (1) | SI2717914T1 (enExample) |
| SM (1) | SMT202000021T1 (enExample) |
| WO (1) | WO2013036309A2 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6530744B2 (ja) * | 2013-05-24 | 2019-06-12 | アイコン バイオサイエンス インコーポレイテッド | 白内障手術後の炎症における徐放性デキサメタゾンの使用 |
| KR102312186B1 (ko) * | 2014-05-08 | 2021-10-14 | 판옵테스 파르마 게스.엠.베.하. | 안 질환 및 장애 치료용 화합물 |
| ES2969514T3 (es) * | 2015-03-18 | 2024-05-21 | Santen Pharmaceutical Co Ltd | Composición farmacéutica de liberación sostenida |
| CA2991015A1 (en) * | 2015-07-01 | 2017-01-05 | Santen Pharmaceutical Co., Ltd. | Depot preparation containing citric acid ester |
| WO2017024027A1 (en) * | 2015-08-03 | 2017-02-09 | Tolmar International Limited | Liquid polymer delivery system for extended administration of drugs |
| PT3352735T (pt) | 2015-09-21 | 2023-10-30 | Teva Pharmaceuticals Int Gmbh | Formulações de olanzapina de libertação sustentada |
| AU2018238136A1 (en) | 2017-03-20 | 2019-11-07 | Teva Pharmaceuticals International Gmbh | Sustained release olanzapine formulations |
| KR101957599B1 (ko) | 2017-10-23 | 2019-03-13 | 김상현 | 훈제 단무지 제조 방법, 이에 의해 제조된 훈제 단무지 |
| WO2019157198A2 (en) | 2018-02-09 | 2019-08-15 | Icon Bioscience, Inc. | Systems, kits and methods for loading and delivering a small volume dose from a syringe |
| EP3787609A4 (en) | 2018-05-01 | 2022-01-05 | Chibi, Inc. | Eye drop formulation and method for sustained delivery of medicament to the retina |
| KR20210003877A (ko) | 2018-05-01 | 2021-01-12 | 치비 인코포레이티드 | 약제를 눈에 비침습적으로 지속 전달하기 위한 액체 데포 |
| EP4153214A4 (en) | 2020-05-22 | 2024-06-26 | Trustees of Boston University | METHODS AND COMPOSITIONS FOR TREATING FIBROTIC DISEASE |
| EP4277661A1 (en) | 2021-01-18 | 2023-11-22 | Anton Frenkel | Pharmaceutical dosage form |
| US20240277654A1 (en) | 2021-07-06 | 2024-08-22 | Mark Hasleton | Treatment of serotonin reuptake inhibitor withdrawal syndrome |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2658432B1 (fr) * | 1990-02-22 | 1994-07-01 | Medgenix Group Sa | Microspheres pour la liberation controlee des substances hydrosolubles et procede de preparation. |
| EP1299048A4 (en) * | 2000-06-28 | 2005-09-28 | Atul J Shukla | BIODEGRADABLE VEHICLES AND SYSTEMS FOR DELIVERY OF BIOLOGICALLY ACTIVE SUBSTANCES |
| TWI353854B (en) * | 2002-06-25 | 2011-12-11 | Alza Corp | Short duration depot formulations |
| US20040001889A1 (en) * | 2002-06-25 | 2004-01-01 | Guohua Chen | Short duration depot formulations |
| CA2527664A1 (en) * | 2003-05-30 | 2004-12-16 | Alza Corporation | Implantable elastomeric depot compositions, uses thereof and method of manufacturing |
| US7727969B2 (en) * | 2003-06-06 | 2010-06-01 | Massachusetts Institute Of Technology | Controlled release nanoparticle having bound oligonucleotide for targeted delivery |
| US7771742B2 (en) * | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
| US8685435B2 (en) * | 2004-04-30 | 2014-04-01 | Allergan, Inc. | Extended release biodegradable ocular implants |
| WO2005110374A1 (en) * | 2004-04-30 | 2005-11-24 | Allergan, Inc. | Intraocular drug delivery systems containing a therapeutic component, a cyclodextrin, and a polymeric component |
| US20080038316A1 (en) * | 2004-10-01 | 2008-02-14 | Wong Vernon G | Conveniently implantable sustained release drug compositions |
| BRPI0516830A (pt) * | 2004-10-01 | 2008-09-23 | Ramscor Inc | composições de droga de liberação sustentada convenientemente implantáveis |
| BRPI0516308A2 (pt) * | 2004-10-04 | 2010-06-15 | Qlt Usa Inc | composição fluida, métodos de tratamento de uma doença ou disfunção, métodos de liberação local ou sistêmica de um agente biológico, implantes, método de formação de um implante, kit de agente biológico e usos de uma composição fluida |
| US8039010B2 (en) | 2006-11-03 | 2011-10-18 | Allergan, Inc. | Sustained release intraocular drug delivery systems comprising a water soluble therapeutic agent and a release modifier |
| US8969415B2 (en) * | 2006-12-01 | 2015-03-03 | Allergan, Inc. | Intraocular drug delivery systems |
| US8821870B2 (en) * | 2008-07-18 | 2014-09-02 | Allergan, Inc. | Method for treating atrophic age related macular degeneration |
| WO2010105093A2 (en) * | 2009-03-12 | 2010-09-16 | Delpor, Inc. | Implantable device for long-term delivery of drugs |
| EP2269663B1 (en) * | 2009-07-03 | 2018-03-07 | Armbruster Biotechnology GmbH | Bone graft and biocomposite |
-
2012
- 2012-06-11 IN IN2384MUN2013 patent/IN2013MN02384A/en unknown
- 2012-06-11 ES ES12829655T patent/ES2761340T3/es active Active
- 2012-06-11 JP JP2014514933A patent/JP6339011B2/ja active Active
- 2012-06-11 MX MX2013014461A patent/MX359119B/es active IP Right Grant
- 2012-06-11 LT LTEP12829655.5T patent/LT2717914T/lt unknown
- 2012-06-11 SM SM20200021T patent/SMT202000021T1/it unknown
- 2012-06-11 BR BR112013031685-3A patent/BR112013031685B1/pt active IP Right Grant
- 2012-06-11 WO PCT/US2012/041950 patent/WO2013036309A2/en not_active Ceased
- 2012-06-11 PT PT128296555T patent/PT2717914T/pt unknown
- 2012-06-11 RS RS20191574A patent/RS60051B1/sr unknown
- 2012-06-11 SI SI201231706T patent/SI2717914T1/sl unknown
- 2012-06-11 HU HUE12829655A patent/HUE047737T2/hu unknown
- 2012-06-11 EP EP12829655.5A patent/EP2717914B1/en active Active
- 2012-06-11 US US14/124,631 patent/US9814773B2/en active Active
- 2012-06-11 HR HRP20192276TT patent/HRP20192276T1/hr unknown
- 2012-06-11 DK DK12829655.5T patent/DK2717914T3/da active
- 2012-06-11 PL PL12829655T patent/PL2717914T3/pl unknown
- 2012-06-11 CA CA2838289A patent/CA2838289C/en active Active
- 2012-06-11 CN CN201280028816.4A patent/CN103945865B/zh active Active
- 2012-06-11 AU AU2012304909A patent/AU2012304909B2/en active Active
- 2012-06-11 KR KR1020147000443A patent/KR20140060274A/ko not_active Withdrawn
-
2020
- 2020-01-17 CY CY20201100042T patent/CY1122771T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL2717914T3 (pl) | 2020-05-18 |
| HRP20192276T1 (hr) | 2020-05-15 |
| AU2012304909A1 (en) | 2013-12-19 |
| SI2717914T1 (sl) | 2020-07-31 |
| RS60051B1 (sr) | 2020-04-30 |
| EP2717914A4 (en) | 2015-05-13 |
| BR112013031685B1 (pt) | 2021-04-06 |
| CN103945865B (zh) | 2016-10-26 |
| EP2717914A2 (en) | 2014-04-16 |
| EP2717914B1 (en) | 2019-10-30 |
| WO2013036309A2 (en) | 2013-03-14 |
| CN103945865A (zh) | 2014-07-23 |
| DK2717914T3 (da) | 2020-01-20 |
| MX359119B (es) | 2018-09-14 |
| MX2013014461A (es) | 2014-05-14 |
| BR112013031685A2 (pt) | 2017-02-07 |
| HUE047737T2 (hu) | 2020-05-28 |
| LT2717914T (lt) | 2020-03-25 |
| IN2013MN02384A (enExample) | 2015-06-12 |
| JP2014516087A (ja) | 2014-07-07 |
| PT2717914T (pt) | 2019-12-18 |
| KR20140060274A (ko) | 2014-05-19 |
| CY1122771T1 (el) | 2021-05-05 |
| US20140140992A1 (en) | 2014-05-22 |
| SMT202000021T1 (it) | 2020-03-13 |
| AU2012304909B2 (en) | 2017-06-08 |
| CA2838289A1 (en) | 2013-03-14 |
| JP6339011B2 (ja) | 2018-06-06 |
| US9814773B2 (en) | 2017-11-14 |
| WO2013036309A3 (en) | 2013-05-10 |
| ES2761340T3 (es) | 2020-05-19 |
| NZ619707A (en) | 2015-01-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2838289C (en) | Sustained release formulations for delivery of proteins to the eye and methods of preparing same | |
| CN101060831B (zh) | 可方便植入的缓释药物组合物 | |
| Tan et al. | Controlled-release nanotherapeutics: State of translation | |
| JP2007535536A (ja) | 高分子含有持続放出眼内インプラントおよび関連方法 | |
| US20150037429A1 (en) | Controlled Release Microparticles | |
| CA2957548A1 (en) | Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof | |
| EP3621588B1 (en) | Ocular compositions | |
| Boddu et al. | Novel nanoparticulate gel formulations of steroids for the treatment of macular edema | |
| JP2021521173A (ja) | 眼内薬物送達用の持続放出微粒子のための方法及び組成物 | |
| EP3976106A1 (en) | Bioerodible polyester polymer implants and related methods of use | |
| Ham et al. | Novel drug delivery methods and approaches for the treatment of retinal diseases | |
| NZ619707B2 (en) | Sustained release formulations for delivery of proteins to the eye and methods of preparing same | |
| HK1196081B (en) | Sustained release formulations for delivery of proteins to the eye and methods of preparing same | |
| HK1196081A (en) | Sustained release formulations for delivery of proteins to the eye and methods of preparing same | |
| Marques et al. | PKPD of PLGA-PEG-PLGA Copolymeric Micelles | |
| CA3124280A1 (en) | Ocular compositions | |
| Kimura et al. | Biodegradable systems | |
| Belin et al. | Recent Innovations in Drug Delivery for Retinal Diseases | |
| WO2024206077A2 (en) | Dosing regimes and combination therapies using archexin for the treatment of cancer | |
| WO2025075991A1 (en) | Cai-loaded bioerodible implant and methods of use thereof | |
| JP2025525881A (ja) | 眼内使用するためのニンテダニブの医薬製剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20150603 |